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113. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis

Author

Fiorito, G., Mccrory, C., Robinson, O., Carmeli, C., Rosales, C. O., Zhang, Y., Colicino, E., Dugue, P. -A., Artaud, F., Mckay, G. J., Jeong, A., Mishra, P. P., Nost, T. H., Krogh, V., Panico, S., Sacerdote, C., Tumino, R., Palli, D., Matullo, G., Guarrera, S., Gandini, M., Bochud, M., Dermitzakis, E., Muka, T., Schwartz, J., Vokonas, P. S., Just, A., Hodge, A. M., Giles, G. G., Southey, M. C., Hurme, M. A., Young, I., Mcknight, A. J., Kunze, S., Waldenberger, M., Peters, A., Schwettmann, L., Lund, E., Baccarelli, A., Milne, R. L., Kenny, R. A., Elbaz, A., Brenner, H., Kee, F., Voortman, T., Probst-Hensch, N., Lehtimaki, T., Elliot, P., Stringhini, S., Vineis, P., Polidoro, S., Alberts, J., Alenius, H., Avendano, M., Baltar, V., Bartley, M., Barros, H., Bellone, M., Berger, E., Blane, D., Candiani, G., Carra, L., Castagne, R., Chadeau-Hyam, M., Cima, S., Clavel-Chapelon, F., Costa, G., Courtin, E., Delpierre, C., D'Errico, A., Dermitzakis, M., Elovainio, M., Elliott, P., Fagherazzi, G., Fraga, S., Gares, V., Gerbouin-Rerolle, P., Giles, G., Goldberg, M., Greco, D., Guessous, I., Haba-Rubio, J., Heinzer, R., Hodge, A., Joost, S., Karimi, M., Kelly-Irving, M., Kahonen, M., Karisola, P., Khenissi, L., Kivimaki, M., Laine, J., Lang, T., Laurent, A., Layte, R., Lepage, B., Lorsch, D., Macguire, F., Machell, G., Mackenbach, J., Marmot, M., de Mestral, C., Miller, C., Milne, R., Muennig, P., Nusselder, W., Petrovic, D., Pilapil, L., Preisig, M., Pulkki-Raback, L., Raitakari, O., Ribeiro, A. I., Ricceri, F., Recalcati, P., Reinhard, E., Valverde, J. R., Saba, S., Santegoets, F., Satolli, R., Simmons, T., Severi, G., Shipley, M. J., Tabak, A., Terhi, V., Tieulent, J., Vaccarella, S., Vigna-Taglianti, F., Vollenweider, P., Vuilleumier, N., Zins, M., Medical Research Council (MRC), Commission of the European Communities, BIOS Consortium, Lifepath consortium, Epidemiology, Dermitzakis, Emmanouil, and Stringhini, Silvia

Subjects
Male, Aging, Geriatrics & Gerontology, Disease, epigenetic clocks, Bioinformatics, 0601 Biochemistry and Cell Biology, DISEASE, Epigenesis, Genetic, Cohort Studies, 0302 clinical medicine, Risk Factors, DNA METHYLATION, media_common, 0303 health sciences, education, Lifepath consortium, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, CARDIOVASCULAR RISK, Aged, Aging/genetics, Aging/psychology, DNA Methylation, Educational Status, Female, Humans, Life Style, Mutation, Social Class, biological aging, socioeconomic position, Longevity, ASSOCIATION, Biological aging, Education, Epigenetic clocks, Socioeconomic position, 3. Good health, WIDE METHYLATION, Aging/genetics/psychology, DNA methylation, Biomarker (medicine), HEALTH, BIOS Consortium, Life Sciences & Biomedicine, Research Paper, Cohort study, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, media_common.quotation_subject, CANCER-RISK, 610 Medicine & health, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, Biology, PERIPHERAL-BLOOD, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic, 360 Social problems & social services, 1112 Oncology and Carcinogenesis, Epigenetics, ddc:613, 030304 developmental biology, Science & Technology, Mechanism (biology), MUTATIONS, dNaM, Socioeconomic Position, Biological Aging, Epigenetic Clocks, Cell Biology, 0606 Physiology, DRIFT, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, 030217 neurology & neurosurgery, Epigenesis
Abstract

Source at https://doi.org/10.18632/aging.101900. Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019
Full Text
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114. Maternal educational inequalities in measured body mass index trajectories in three European countries

Author

Mccrory, C., Leahy, S., Ribeiro, A. I., Fraga, S., Barros, H., Avendano, M., Vineis, P., Layte, R., Alenius, H., Baglietto, L., Bartley, M., Bellone, M., Berger, E., Bochud, M., Candiani, G., Carmeli, C., Carra, L., Castagne, R., Chadeau-Hyam, M., Cima, S., Costa, G., Courtin, E., Delpierre, C., D'Errico, A., Donkin, A., Dugue, P. -A., Elliott, P., Fagherazzi, G., Fiorito, G., Gandini, Martina, Gares, V., Gerbouin-Rerrolle, P., Giles, G., Goldberg, M., Greco, D., Guida, F., Hodge, A., Karimi, M., Karisola, P., Kelly, M., Kivimaki, M., Laine, J., Lang, T., Laurent, A., Lepage, B., Lorsch, D., Machell, G., Mackenbach, J., Marmot, M., Milne, David Robert, Muennig, P., Nusselder, W., Petrovic, D., Polidoro, S., Preisig, M., Recalcati, P., Reinhard, E., Ricceri, F., Robinson, O., Jose, R., Severi, PAULA GABRIELA, Simmons, T., Stringhini, S., Terhi, V., Than, J., Vergnaud, A. -C., Vigna-Taglianti, F., Vollenweider, P., Zins, M., Epidemiology, Public Health, HRB, and ERC

Subjects
Male, Pediatric Obesity, obesity, Adolescent, Inequality, Epidemiology, body mass index, children, cohort study, growth curves, overweight, social inequalities, media_common.quotation_subject, Social gradient, Mothers, Prospective data, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Prevalence, medicine, Humans, Social inequality, Prospective Studies, Child, media_common, 2. Zero hunger, 030219 obstetrics & reproductive medicine, Portugal, business.industry, 4. Education, Health Status Disparities, medicine.disease, Obesity, United Kingdom, Millennium Cohort Study (United States), Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Educational Status, Female, business, Ireland, Body mass index, Demography
Abstract

BACKGROUND: Social inequalities in the prevalence of childhood overweight and obesity are well-established, but less is known about when the social gradient first emerges and how it evolves across childhood and adolescence.OBJECTIVE: This study examines maternal education differentials in children's body mass trajectories in infancy, childhood and adolescence using data from four contemporary European child cohorts.METHODS: Prospective data on children's body mass index (BMI) were obtained from four cohort studies-Generation XXI (G21-Portugal), Growing Up in Ireland (GUI) infant and child cohorts, and the Millennium Cohort Study (MCS-UK)-involving a total sample of 41,399 children and 120,140 observations. Children's BMI trajectories were modelled by maternal education level using mixed-effect models.RESULTS: Maternal educational inequalities in children's BMI were evident as early as three years of age. Children from lower maternal educational backgrounds were characterised by accelerated BMI growth, and the extent of the disparity was such that boys from primary-educated backgrounds measured 0.42 kg/m2 (95% CI 0.24, 0.60) heavier at 7 years of age in G21, 0.90 kg/m2 (95% CI 0.60, 1.19) heavier at 13 years of age in GUI and 0.75 kg/m2 (95% CI 0.52, 0.97) heavier in MCS at 14 years of age. The corresponding figures for girls were 0.71 kg/m2 (95% CI 0.50, 0.91), 1.31 kg/m2 (95% CI 1.00, 1.62) and 0.76 kg/m2 (95% CI 0.53, 1.00) in G21, GUI and MCS, respectively.CONCLUSIONS: Maternal education is a strong predictor of BMI across European nations. Socio-economic differentials emerge early and widen across childhood, highlighting the need for early intervention.

Published
2019
Full Text
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116. Son Thang: An American War Crime.

Author

Everett, Robinson O.

Subjects
Son Thang: An American War Crime (Book), Books -- Book reviews
Abstract

Son Thang: An American War Crime. By Gary D. Solis. Annapolis: Naval Institute Press. 1997. Pp. xix, 299. $29.95. The subject of war crimes is now receiving significant attention. On [...]

Published
1998

122. CASSETTE—clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: Study protocol for a randomised controlled trial

Author

Dotel, R., Tong, S.Y.C., Bowen, A., Nelson, J.N., O’Sullivan, M.V.N., Campbell, A.J., McMullan, B.J., Britton, P.N., Francis, J.R., Eisen, D.P., Robinson, O., Manning, L., Davis, J.S., Dotel, R., Tong, S.Y.C., Bowen, A., Nelson, J.N., O’Sullivan, M.V.N., Campbell, A.J., McMullan, B.J., Britton, P.N., Francis, J.R., Eisen, D.P., Robinson, O., Manning, L., and Davis, J.S.

Abstract

Background Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking. Methods An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to β-lactams or lincosamides will be excluded. The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed. Discussion This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12617001416381p. Registered o

Published
2019

123. CASSETTE-clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: Study protocol for a randomised controlled trial

Author

Dotel, R, Tong, SYC, Bowen, A, Nelson, JN, O'sullivan, MVN, Campbell, AJ, McMullan, BJ, Britton, PN, Francis, JR, Eisen, DP, Robinson, O, Manning, L, Davis, JS, Dotel, R, Tong, SYC, Bowen, A, Nelson, JN, O'sullivan, MVN, Campbell, AJ, McMullan, BJ, Britton, PN, Francis, JR, Eisen, DP, Robinson, O, Manning, L, and Davis, JS

Abstract

Background: Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking. Methods: An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to β-lactams or lincosamides will be excluded. The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed. Discussion: This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT.

Published
2019

124. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.

Author

Kee F., Rosales C.O., Zhang Y., Colicino E., Dugue P.-A., Artaud F., McKay G.J., Jeong A., Mishra P.P., Elbaz A., Brenner H., Carmeli C., Voortman T., Probst-Hensch N., Lehtimaki T., Elliot P., Stringhini S., Vineis P., Polidoro S., Fiorito G., McCrory C., Robinson O., Nost T.H., Krogh V., Panico S., Sacerdote C., Tumino R., Palli D., Matullo G., Guarrera S., Gandini M., Bochud M., Dermitzakis E., Muka T., Schwartz J., Vokonas P.S., Just A., Hodge A.M., Giles G.G., Southey M.C., Hurme M.A., Young I., McKnight A.J., Kunze S., Waldenberger M., Peters A., Schwettmann L., Lund E., Baccarelli A., Milne R.L., Kenny R.A., Kee F., Rosales C.O., Zhang Y., Colicino E., Dugue P.-A., Artaud F., McKay G.J., Jeong A., Mishra P.P., Elbaz A., Brenner H., Carmeli C., Voortman T., Probst-Hensch N., Lehtimaki T., Elliot P., Stringhini S., Vineis P., Polidoro S., Fiorito G., McCrory C., Robinson O., Nost T.H., Krogh V., Panico S., Sacerdote C., Tumino R., Palli D., Matullo G., Guarrera S., Gandini M., Bochud M., Dermitzakis E., Muka T., Schwartz J., Vokonas P.S., Just A., Hodge A.M., Giles G.G., Southey M.C., Hurme M.A., Young I., McKnight A.J., Kunze S., Waldenberger M., Peters A., Schwettmann L., Lund E., Baccarelli A., Milne R.L., and Kenny R.A.

Abstract

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019

125. Maternal educational inequalities in measured body mass index trajectories in three European countries

Author

McCrory, C, Leahy, S, Ribeiro, AI, Fraga, S, Barros, H, Avendano, M, Vineis, P, Layte, R, Alenius, H, Baglietto, L, Bartley, M, Bellone, M, Berger, E, Bochud, M, Candiani, G, Carmeli, C, Carra, L, Castagne, R, Chadeau-Hyam, M, Cima, S, Costa, G, Courtin, E, Delpierre, C, D'Errico, A, Donkin, A, Dugue, P-A, Elliott, P, Fagherazzi, G, Fiorito, G, Gandini, M, Gares, V, Gerbouin-Rerrolle, P, Giles, G, Goldberg, M, Greco, D, Guida, F, Hodge, A, Karimi, M, Karisola, P, Kelly, M, Kivimaki, M, Laine, J, Lang, T, Laurent, A, Lepage, B, Lorsch, D, Machell, G, Mackenbach, J, Marmot, M, Milne, R, Muennig, P, Nusselder, W, Petrovic, D, Polidoro, S, Preisig, M, Recalcati, P, Reinhard, E, Ricceri, F, Robinson, O, Valverde, JR, Severi, G, Simmons, T, Stringhini, S, Terhi, V, Than, J, Vergnaud, A-C, Vigna-Taglianti, F, Vollenweider, P, Zins, M, McCrory, C, Leahy, S, Ribeiro, AI, Fraga, S, Barros, H, Avendano, M, Vineis, P, Layte, R, Alenius, H, Baglietto, L, Bartley, M, Bellone, M, Berger, E, Bochud, M, Candiani, G, Carmeli, C, Carra, L, Castagne, R, Chadeau-Hyam, M, Cima, S, Costa, G, Courtin, E, Delpierre, C, D'Errico, A, Donkin, A, Dugue, P-A, Elliott, P, Fagherazzi, G, Fiorito, G, Gandini, M, Gares, V, Gerbouin-Rerrolle, P, Giles, G, Goldberg, M, Greco, D, Guida, F, Hodge, A, Karimi, M, Karisola, P, Kelly, M, Kivimaki, M, Laine, J, Lang, T, Laurent, A, Lepage, B, Lorsch, D, Machell, G, Mackenbach, J, Marmot, M, Milne, R, Muennig, P, Nusselder, W, Petrovic, D, Polidoro, S, Preisig, M, Recalcati, P, Reinhard, E, Ricceri, F, Robinson, O, Valverde, JR, Severi, G, Simmons, T, Stringhini, S, Terhi, V, Than, J, Vergnaud, A-C, Vigna-Taglianti, F, Vollenweider, P, and Zins, M

Abstract

BACKGROUND: Social inequalities in the prevalence of childhood overweight and obesity are well-established, but less is known about when the social gradient first emerges and how it evolves across childhood and adolescence. OBJECTIVE: This study examines maternal education differentials in children's body mass trajectories in infancy, childhood and adolescence using data from four contemporary European child cohorts. METHODS: Prospective data on children's body mass index (BMI) were obtained from four cohort studies-Generation XXI (G21-Portugal), Growing Up in Ireland (GUI) infant and child cohorts, and the Millennium Cohort Study (MCS-UK)-involving a total sample of 41,399 children and 120,140 observations. Children's BMI trajectories were modelled by maternal education level using mixed-effect models. RESULTS: Maternal educational inequalities in children's BMI were evident as early as three years of age. Children from lower maternal educational backgrounds were characterised by accelerated BMI growth, and the extent of the disparity was such that boys from primary-educated backgrounds measured 0.42 kg/m2 (95% CI 0.24, 0.60) heavier at 7 years of age in G21, 0.90 kg/m2 (95% CI 0.60, 1.19) heavier at 13 years of age in GUI and 0.75 kg/m2 (95% CI 0.52, 0.97) heavier in MCS at 14 years of age. The corresponding figures for girls were 0.71 kg/m2 (95% CI 0.50, 0.91), 1.31 kg/m2 (95% CI 1.00, 1.62) and 0.76 kg/m2 (95% CI 0.53, 1.00) in G21, GUI and MCS, respectively. CONCLUSIONS: Maternal education is a strong predictor of BMI across European nations. Socio-economic differentials emerge early and widen across childhood, highlighting the need for early intervention.

Published
2019

126. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis

Author

Fiorito, G, McCrory, C, Robinson, O, Carmeli, C, Rosales, CO, Zhang, Y, Colicino, E, Dugue, P-A, Artaud, F, Mckay, GJ, Jeong, A, Mishra, PP, Nost, TH, Krogh, V, Panico, S, Sacerdote, C, Tumino, R, Palli, D, Matullo, G, Guarrera, S, Gandini, M, Bochud, M, Dermitzakis, E, Muka, T, Schwartz, J, Vokonas, PS, Just, A, Hodge, AM, Giles, GG, Southey, MC, Hurme, MA, Young, I, McKnight, AJ, Kunze, S, Waldenberger, M, Peters, A, Schwettmann, L, Lund, E, Baccarelli, A, Milne, RL, Kenny, RA, Elbaz, A, Brenner, H, Kee, F, Voortman, T, Probst-Hensch, N, Lehtimaki, T, Elliot, P, Stringhini, S, Vineis, P, Polidoro, S, Alberts, J, Alenius, H, Avendano, M, Baltar, V, Bartley, M, Barros, H, Bellone, M, Berger, E, Blane, D, Candiani, G, Carra, L, Castagne, R, Chadeau-Hyam, M, Cima, S, Clavel-Chapelon, F, Costa, G, Courtin, E, Delpierre, C, D'Errico, A, Manolis, Dermitzakis, Elovainio, M, Elliott, P, Fagherazzi, G, Fraga, S, Gares, V, Gerbouin-Rerolle, P, Giles, G, Goldberg, M, Greco, D, Guessous, I, Haba-Rubio, J, Heinzer, R, Hodge, A, Joost, S, Karimi, M, Kelly-Irving, M, Kahonen, M, Karisola, P, Khenissi, L, Kivimaki, M, Laine, J, Lang, T, Laurent, A, Layte, R, Lepage, B, Lorsch, D, MacGuire, F, Machell, G, Mackenbach, J, Marmot, M, de Mestral, C, Miller, C, Milne, R, Muennig, P, Nusselder, W, Petrovic, D, Lourdes, Pilapil, Preisig, M, Pulkki-Raback, L, Raitakari, O, Ribeiro, AI, Ricceri, F, Recalcati, P, Reinhard, E, Valverde, JR, Saba, S, Santegoets, F, Satolli, R, Simmons, T, Severi, G, Shipley, MJ, Tabak, A, Terhi, V, Tieulent, J, Vaccarella, S, Vigna-Taglianti, F, Vollenweider, P, Vuilleumier, N, Zins, M, Fiorito, G, McCrory, C, Robinson, O, Carmeli, C, Rosales, CO, Zhang, Y, Colicino, E, Dugue, P-A, Artaud, F, Mckay, GJ, Jeong, A, Mishra, PP, Nost, TH, Krogh, V, Panico, S, Sacerdote, C, Tumino, R, Palli, D, Matullo, G, Guarrera, S, Gandini, M, Bochud, M, Dermitzakis, E, Muka, T, Schwartz, J, Vokonas, PS, Just, A, Hodge, AM, Giles, GG, Southey, MC, Hurme, MA, Young, I, McKnight, AJ, Kunze, S, Waldenberger, M, Peters, A, Schwettmann, L, Lund, E, Baccarelli, A, Milne, RL, Kenny, RA, Elbaz, A, Brenner, H, Kee, F, Voortman, T, Probst-Hensch, N, Lehtimaki, T, Elliot, P, Stringhini, S, Vineis, P, Polidoro, S, Alberts, J, Alenius, H, Avendano, M, Baltar, V, Bartley, M, Barros, H, Bellone, M, Berger, E, Blane, D, Candiani, G, Carra, L, Castagne, R, Chadeau-Hyam, M, Cima, S, Clavel-Chapelon, F, Costa, G, Courtin, E, Delpierre, C, D'Errico, A, Manolis, Dermitzakis, Elovainio, M, Elliott, P, Fagherazzi, G, Fraga, S, Gares, V, Gerbouin-Rerolle, P, Giles, G, Goldberg, M, Greco, D, Guessous, I, Haba-Rubio, J, Heinzer, R, Hodge, A, Joost, S, Karimi, M, Kelly-Irving, M, Kahonen, M, Karisola, P, Khenissi, L, Kivimaki, M, Laine, J, Lang, T, Laurent, A, Layte, R, Lepage, B, Lorsch, D, MacGuire, F, Machell, G, Mackenbach, J, Marmot, M, de Mestral, C, Miller, C, Milne, R, Muennig, P, Nusselder, W, Petrovic, D, Lourdes, Pilapil, Preisig, M, Pulkki-Raback, L, Raitakari, O, Ribeiro, AI, Ricceri, F, Recalcati, P, Reinhard, E, Valverde, JR, Saba, S, Santegoets, F, Satolli, R, Simmons, T, Severi, G, Shipley, MJ, Tabak, A, Terhi, V, Tieulent, J, Vaccarella, S, Vigna-Taglianti, F, Vollenweider, P, Vuilleumier, N, and Zins, M

Abstract

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019

127. Barriers and facilitators to implementing Dementia Care Mapping in Care Homes: Results from the DCM EPIC Trial process evaluation

Author

Griffiths, A, Kelley, R, Garrod, L, Perfect, D, Robinson, O, Shoesmith, E, McDermid, J, Burnley, N, Surr, CA, Griffiths, A, Kelley, R, Garrod, L, Perfect, D, Robinson, O, Shoesmith, E, McDermid, J, Burnley, N, and Surr, CA

Abstract

Background: Psychosocial person-centred interventions are considered best practice for addressing complex behaviours and care needs such as agitation and anxiety, and for improving the quality of life of people with dementia in care homes. Dementia Care Mapping (DCM™) is an established practice development tool and process aimed to help care home staff deliver more person-centred care. To date, few studies have evaluated the efficacy of DCM™ and have found mixed results. These results are suggested to be the outcome of intervention implementation, which may be impacted by a range of factors. This study reports the barriers and facilitators to DCM™ implementation in care homes found during the process evaluation conducted as part of a randomized controlled trial. Methods: Eighteen of the 31 DCM™ intervention care homes were recruited to participate in the embedded process evaluation. Semi-structured interviews were conducted with 83 participants, comprising care home managers, trained DCM™ users (mappers), expert external mappers, staff members, relatives, and residents. Results: Barriers and facilitators to DCM™ implementation were found at the mapper level (e.g. motivation and confidence), the DCM™ intervention level (e.g. understanding of DCM™) and the care home level (e.g. staffing issues, manager support). Further barriers caused by the burden of trial participation were also identified (e.g. additional paperwork). Conclusions: Implementing DCM™ is complex and a greater consideration of potential barriers and facilitators in planning future studies and in practice could help improve implementation. Trial Registation: Current Controlled Trials ISRCTN82288852, registered 16/01/2014

Published
2019

129. Functionalized Zea Mays Cob (FZMC) as low-cost agrowaste for effective adsorption of malachite green dyes data set

Author

Robinson O. David, J. O. Ojediran, Stephen O. Aniyi, and Adewumi O. Dada

Subjects
010405 organic chemistry, Sorption, General Chemistry, 010402 general chemistry, 01 natural sciences, Bulk density, Zea mays, 0104 chemical sciences, chemistry.chemical_compound, Adsorption, chemistry, Physisorption, Freundlich equation, Malachite green, Water content, Nuclear chemistry
Abstract

This dataset article presents the effective adsorption of Malachite Green (MG) dyes onto FZMC as low-cost agro-waste. The physicochemical parameters data of the FZMC (1329 m2/g surface area; 12% moisture content; 0.9% loss of mass on ignition; 0.386 g/cm3 bulk density) showed its suitability for sorption. Favorable adsorption of MG dye in a batch technique was achieved at pH 8, 120 min contact time through 100 – 600 ppm concentrations. With R2>0.98, the Pseudo second-order model best represented kinetic data. The mechanism was better represented by the intraparticle diffusion model. Equilibrium data were best described by Freundlich and confirmed by Halsey isotherm with R2>0.97 and physisorption nature of the d -R isotherm model (E (J/mol)

Published
2020
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132. Evaluating the effectiveness of the National Health Insurance Fund in providing financial protection to households with hypertension and diabetes patients in Kenya

Author

Robinson Oyando, Vincent Were, Hillary Koros, Richard Mugo, Jemima Kamano, Anthony Etyang, Adrianna Murphy, Kara Hanson, Pablo Perel, and Edwine Barasa

Subjects
Non-communicable diseases, Health expenditure, Financial risk protection, Health insurance, Kenya, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Non-communicable diseases (NCDs) can impose a substantial financial burden to households in the absence of an effective financial risk protection mechanism. The national health insurance fund (NHIF) has included NCD services in its national scheme. We evaluated the effectiveness of NHIF in providing financial risk protection to households with persons living with hypertension and/or diabetes in Kenya. Methods We carried out a prospective cohort study, following 888 households with at least one individual living with hypertension and/or diabetes for 12 months. The exposure arm comprised households that are enrolled in the NHIF national scheme, while the control arm comprised households that were not enrolled in the NHIF. Study participants were drawn from two counties in Kenya. We used the incidence of catastrophic health expenditure (CHE) as the outcome of interest. We used coarsened exact matching and a conditional logistic regression model to analyse the odds of CHE among households enrolled in the NHIF compared with unenrolled households. Socioeconomic inequality in CHE was examined using concentration curves and indices. Results We found strong evidence that NHIF-enrolled households spent a lower share (12.4%) of their household budget on healthcare compared with unenrolled households (23.2%) (p = 0.004). While households that were enrolled in NHIF were less likely to incur CHE, we did not find strong evidence that they are better protected from CHE compared with households without NHIF (OR = 0.67; p = 0.47). The concentration index (CI) for CHE showed a pro-poor distribution (CI: -0.190, p

Published
2023
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133. Instantaneous topology of the unsteady leading-edge vortex at high angle of attack

Author

Magness, C., Robinson, O., and Rockwell, D.

Subjects
Flow visualization -- Observations, Fluid dynamics -- Research, Aerospace and defense industries, Business
Abstract

A new topological structure for flow over a delta wing undergoing transient pitching maneuvers at high angle of attack is not similar to the traditional topology for stationary wings at low angle of attack. An outward spiral motion is exhibited by the leading edge vortex corresponding to a significant change in the entire crossflow topology. Due to this major change in the nature of the leading-edge vortex, an unstable focus is induced, possibly by the rapid, transient pitch-up motion of the wing which increases the compression of the core vortex filament.

Published
1993

134. Control of vortices on a delta wing by leading-edge injection

Author

Gu, W., Robinson, O., and Rockwell, D.

Subjects
Airplanes -- Wings, Aerospace and defense industries, Business
Abstract

The flow past delta wings and bodies of revolution at a high angle of attack results in vortex disruption and vortex asymmetry and in the loss of control of the aircraft. The employment of steady injection procedures may augment the balance of the leading-edge vortices and also enhance the lift/moment on the wing and the body. The employment of techniques such as steady blowing, steady suction or suction-blowing at a tangent from the edge of the wing will reduce the chances of vortex breakdown and stalling. However, the application and effectiveness of these techniques is dependent on several factors such as the angle of attack, sweep attack and the thickness of the wing.

Published
1993

138. Pattern of Presentation of Primary Bone Tumors in Nnewi, South-East Nigeria

Author

Ugezu, Anthony I., Imo, Chima O, Ihegihu, Chima C, and Ofiaeli, Robinson O

Subjects
Primary bone tumors, Epidemiology, Bone lesions, Histologic types, Nnewi
Abstract

Background: Primary bone tumors are rare and there is paucity of information on the pattern of its presentation in our environment. There is less thought given to it by the patients and sometimes medical personnel, leading to late presentation, late diagnosis and subsequent adverse sequelae. Objective: The aim of this study was to determine the pattern of presentation of primary bone tumors in Nnewi South Eastern Nigeria Methodology: This was a retrospective hospital based study. Records of patients with histological confirmed primary bone tumors seen between January 2012 and December 2016 were reviewed. Patient’s bio-data, symptoms, time of presentation to hospital, anatomical sites involved and tumor histological types were obtained and analyzed. Results: Thirty one (31) patients were studied. There were more males than females (1.1:1). The mean age of the patients was 38.8± 1.2 years with a range of 4-73 years. The most common malignant bone tumor seen was Osteosarcoma. Pain was the most common symptom and the interval between onset of symptom and presentation was 36.9 months with a range of 2-168 months. The distal femur is the most commonly involved anatomical site. Conclusion: Primary bone tumors are not very common, but more patients with malignant tumors were seen in our environment. Most patients presented with pain and swelling. Medical personnel are advised to have a high index of suspicion when evaluating patients with these symptoms.Key words: Primary bone tumors, Epidemiology, Bone lesions, Histologic types, Nnewi.

Published
2018

139. Use of External Fixator in Achieving Early Osseous Fusion in Boyd’s Amputation of the Ankle – A Review of Two Cases

Author

Ofiaeli, Robinson O, Ndukwu, Chibuzo U, and Ofiaeli, Chinenye O

Subjects
Calcaneus, Disarticulation, Diabetic foot, Gangrene
Abstract

Boyd amputation refers to amputation at the level of the ankle with preservation of the calcaneus and heel pad with consequent fixation of the calcaneus to the tibia. This allows for complete weight bearing and provides stabilization of the heel pad. It is a technically more difficult procedure to perform than the Syme amputation which is a more popular procedure done in ankle disarticulations. The aim of this report is to document our experience with the use of external fixators to achieve osseous union in the management of diabetic foot gangrene. Two cases of diabetic foot gangrene were managed successfully by Boyd’s amputation using external fixators to achieve compression, osseous integration and union. This procedure will be quite useful in developing countries where prosthesis utilization is poor and expensive as obtains in higher level amputations.Key words: Calcaneus, Disarticulation, Diabetic foot, Gangrene

Published
2018

140. Delivering holistic low level support to intellectually able autistic adults: Lessons from an advocacy, information and mentoring service

Author

Southby, K, Robinson, O, and Cork, W

Abstract

There are many intellectually able autistic adults who would like to have a better quality of life but who struggle to access advice and support from traditional services. This situation leads to emotional distress and poor outcomes for these individuals and their families and society generally. So services such as the Leeds AIM (Advocacy, Information and Mentoring) service described in this paper have great potential in enhancing the lives of this group and in educating mainstream services on how advice and support might be adjusted to allow better access. In addition, creating good spaces for autistic adults offers opportunities for social contact and friendships with like-minded peers both within and outside the service

Published
2018

141. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with e coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance

Author

Harris, P. N. A., Tambyah, P. A., Lye, D. C., Mo, Y., Lee, T. H., Yilmaz, M., Alenazi, T. H., Arabi, Y., Falcone, M., Bassetti, M., Righi, E., Rogers, B. A., Kanj, S., Bhally, H., Iredell, J., Mendelson, M., Boyles, T. H., Looke, D., Miyakis, S., Walls, G., Al Khamis, M., Zikri, A., Crowe, A., Ingram, P., Daneman, N., Griffin, P., Athan, E., Lorenc, P., Baker, P., Roberts, L., Beatson, S. A., Peleg, A. Y., Harris-Brown, T., Paterson, D. L., Mcnamara, J., Sieler, R., Garlick, J., Costa, J., Roney, J., Pratt, N., Tabaja, H., Kmeid, J., Tayyar, R., El Zein, S., Jones, S., Cowan, R., Tai, A., Lin, B., Rad, B., Macmorran, E., Pollard, J., Dinleyici, R., Istanbullu, A., Ceylan, B., Mert, A., Hashhoush, M., Dalwi, T., Korman, T., Azzam, R., Birrell, M., Hughes, C., Khan, S., Lau, J., Lee, L., Lim, K., Lin, Y. D., Lister, D., New, D., Rafiei, N., Stewart, J., Trad, M. A., Aye Yeung, V., Mcbride, S., Holland, D., Hopkins, C., Luey, C., Taylor, S., Morpeth, S., Finney, M., Martin, M., Holland, U., Ali, J., Jureen, R., Underwood, N., Henderson, A., Runnegar, N., Slavin, M., Robinson, O., Rishu, A., Shawkat, S., Fish, J., Chin Liew, K., Newton, P., Merelli, M., Carnelutti, A., Ussai, S., Pecori, D., Izharuddin, E., Young, B., Ding, Y., Ram, R., Kelly, J., Joshi, N., Richards, G., Smith, O., Alli, A., Vermeulen, I., Wright, B., Grey, C., Stewart, A., Reddy, D., Wasserman, S., Richi, H., Sultana, K., Alanazi, N., Bin Awad, E., Franzetti, F., Stolz, A., De Kock, E., Magongoa, T., Dutoit, M., Russo, A., Dentone, C., Eisen, D., and Heyer, L.

Subjects
Adult, Male, Piperacillin, Tazobactam Drug Combination, Ceftriaxone, Drug Resistance, Bacterial, Penicillanic Acid, Bacteremia, Meropenem, Middle Aged, Anti-Bacterial Agents, Klebsiella Infections, Klebsiella pneumoniae, Cause of Death, Escherichia coli, Humans, Female, Thienamycins, Aged, Drug Resistance, Bacterial, Escherichia coli Infections, Piperacillin, Tazobactam Drug Combination
Published
2018

143. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with e coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance.

Author

Pollard J., Arabi Y., Athan E., Lorenc P., Baker P., Roberts L., Beatson S.A., Peleg A.Y., Harris-Brown T., Paterson D.L., McNamara J., Sieler R., Garlick J., Costa J., Roney J., Pratt N., Tabaja H., Kmeid J., Tayyar R., El Zein S., Jones S., Cowan R., Lin B., Rad B., MacMorran E., Dinleyici R., Istanbullu A., Ceylan B., Mert A., Hashhoush M., Dalwi T., Korman T., Azzam R., Birrell M., Hughes C., Khan S., Lau J., Lee L., Lim K., Lin Y.D., Lister D., New D., Rafiei N., Stewart J., Tai A., Trad M.A., Aye Yeung V., McBride S., Holland D., Hopkins C., Luey C., Taylor S., Morpeth S., Finney M., Martin M., Holland U., Ali J., Jureen R., Underwood N., Henderson A., Runnegar N., Slavin M., Robinson O., Rishu A., Shawkat S., Fish J., Chin Liew K., Newton P., Merelli M., Carnelutti A., Ussai S., Pecori D., Izharuddin E., Young B., Ding Y., Ram R., Kelly J., Joshi N., Richards G., Smith O., Alli A., Vermeulen I., Wright B., Grey C., Stewart A., Reddy D., Wasserman S., Richi H., Sultana K., Alanazi N., Bin Awad E., Franzetti F., Stolz A., De Kock E., Magongoa T., Dutoit M., Russo A., Dentone C., Eisen D., Heyer L., Harris P.N.A., Tambyah P.A., Lye D.C., Mo Y., Lee T.H., Yilmaz M., Alenazi T.H., Falcone M., Bassetti M., Righi E., Rogers B.A., Kanj S., Bhally H., Iredell J., Mendelson M., Boyles T.H., Looke D., Miyakis S., Walls G., Al Khamis M., Zikri A., Crowe A., Ingram P., Daneman N., Griffin P., Pollard J., Arabi Y., Athan E., Lorenc P., Baker P., Roberts L., Beatson S.A., Peleg A.Y., Harris-Brown T., Paterson D.L., McNamara J., Sieler R., Garlick J., Costa J., Roney J., Pratt N., Tabaja H., Kmeid J., Tayyar R., El Zein S., Jones S., Cowan R., Lin B., Rad B., MacMorran E., Dinleyici R., Istanbullu A., Ceylan B., Mert A., Hashhoush M., Dalwi T., Korman T., Azzam R., Birrell M., Hughes C., Khan S., Lau J., Lee L., Lim K., Lin Y.D., Lister D., New D., Rafiei N., Stewart J., Tai A., Trad M.A., Aye Yeung V., McBride S., Holland D., Hopkins C., Luey C., Taylor S., Morpeth S., Finney M., Martin M., Holland U., Ali J., Jureen R., Underwood N., Henderson A., Runnegar N., Slavin M., Robinson O., Rishu A., Shawkat S., Fish J., Chin Liew K., Newton P., Merelli M., Carnelutti A., Ussai S., Pecori D., Izharuddin E., Young B., Ding Y., Ram R., Kelly J., Joshi N., Richards G., Smith O., Alli A., Vermeulen I., Wright B., Grey C., Stewart A., Reddy D., Wasserman S., Richi H., Sultana K., Alanazi N., Bin Awad E., Franzetti F., Stolz A., De Kock E., Magongoa T., Dutoit M., Russo A., Dentone C., Eisen D., Heyer L., Harris P.N.A., Tambyah P.A., Lye D.C., Mo Y., Lee T.H., Yilmaz M., Alenazi T.H., Falcone M., Bassetti M., Righi E., Rogers B.A., Kanj S., Bhally H., Iredell J., Mendelson M., Boyles T.H., Looke D., Miyakis S., Walls G., Al Khamis M., Zikri A., Crowe A., Ingram P., Daneman N., and Griffin P.

Abstract

IMPORTANCE Extended-spectrum beta-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum beta-lactamase producers. OBJECTIVES To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. DESIGN, SETTING, AND PARTICIPANTS Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. INTERVENTIONS Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. RESULTS Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6

Published
2018

144. Assessment of metabolic phenotypic variability in children's urine using H-1 NMR spectroscopy

Author

Maitre, L, Lau, C-HE, Vizcaino, E, Robinson, O, Casas, M, Siskos, AP, Want, EJ, Athersuch, T, Slama, R, Vrijheid, M, Keun, HC, Coen, M, and Commission of the European Communities

Subjects
Multidisciplinary Sciences, Science & Technology, STRESS, PLASMA, CARDIOVASCULAR-DISEASE, BIOMARKERS, Science & Technology - Other Topics, POPULATIONS, SPECTRA, CONSUMPTION, PROFILES, ASSOCIATION, RHYTHMS
Abstract

The application of metabolic phenotyping in clinical and epidemiological studies is limited by a poor understanding of inter-individual, intra-individual and temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we characterised short-term variability in urinary metabolites measured from 20 children aged 8–9 years old. Daily spot morning, night-time and pooled (50:50 morning and night-time) urine samples across six days (18 samples per child) were analysed, and 44 metabolites quantified. Intraclass correlation coefficients (ICC) and mixed effect models were applied to assess the reproducibility and biological variance of metabolic phenotypes. Excellent analytical reproducibility and precision was demonstrated for the 1H NMR spectroscopic platform (median CV 7.2%). Pooled samples captured the best inter-individual variability with an ICC of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate, 3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate exhibited the highest stability with over 50% of variance specific to the child. The pooled sample was shown to capture the most inter-individual variance in the metabolic phenotype, which is of importance for molecular epidemiology study design. A substantial proportion of the variation in the urinary metabolome of children is specific to the individual, underlining the potential of such data to inform clinical and exposome studies conducted early in life.

Published
2017

145. Control of leading-edge vortices on a delta wing

Author

Magness, C, Robinson, O, and Rockwell, D

Subjects
Aerodynamics
Abstract

The unsteady flow structure of leading-edge vortices on a delta wing has been investigated using new types of experimental techniques, in order to provide insight into the consequences of various forms of active control. These investigations involve global control of the entire wing and local control applied at crucial locations on or adjacent to the wing. Transient control having long and short time-scales, relative to the convective time-scale C/U(sub infinity), allows substantial modification of the unsteady and time-mean flow structure. Global control at long time-scale involves pitching the wing at rates an order of magnitude lower than the convective time-scale C/U(sub infinity), but at large amplitudes. The functional form of the pitching maneuver exerts a predominant influence on the trajectory of the feeding sheet, the instantaneous vorticity distribution, and the instantaneous location of vortex breakdown. Global control at short time-scales of the order of the inherent frequency of the shear layer separating from the leading-edge and the natural frequency of vortex breakdown shows that 'resonant' response of the excited shear layer-vortex breakdown system is attainable. The spectral content of the induced disturbance is preserved not only across the entire core of the vortex, but also along the axis of the vortex into the region of vortex breakdown. This unsteady modification results in time-mean alteration of the axial and swirl velocity fields and the location of vortex breakdown. Localized control at long and short time-scales involves application of various transient forms of suction and blowing using small probes upstream and downstream of the location of vortex breakdown, as well as distributed suction and blowing along the leading-edge of the wing applied in a direction tangential to the feeding sheet. These local control techniques can result in substantial alteration of the location of vortex breakdown; in some cases, it is possible to accomplish this without net mass addition to the flow field.

Published
1992

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