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1. Induced protein expression in Leptospira spp. and its application to CRISPR/Cas9 mutant generation.

Author

Fernandes, L. G. V., Nascimento, A. L. T. O., and Nally, J. E.

Abstract

Expanding the genetic toolkit for Leptospira spp. is a crucial step toward advancing our understanding of the biology and virulence of these atypical bacteria. Pathogenic Leptospira are responsible for over 1 million human leptospirosis cases annually and significantly impact domestic animals. Bovine leptospirosis causes substantial financial losses due to abortion, stillbirths, and suboptimal reproductive performance. The advent of the CRISPR/Cas9 system has marked a turning point in genetic manipulation, with applications across multiple Leptospira species. However, incorporating controlled protein expression into existing genetic tools could further expand their utility. We developed and demonstrated the functionality of IPTG-inducible heterologous protein expression in Leptospira spp. This system was applied for regulated expression of dead Cas9 (dCas9) to generate knockdown mutants, and Cas9 to produce knockout mutants by inducing double-strand breaks (DSB) into desired targets. IPTG-induced dCas9 expression enabled validation of essential genes and non-coding RNAs. Additionally, IPTG-controlled Cas9 expression combined with a constitutive non-homologous end-joining (NHEJ) system allowed for successful recovery of knockout mutants, even in the absence of IPTG. These newly controlled protein expression systems will advance studies on the basic biology and virulence of Leptospira, as well as facilitate knockout mutant generation for improved veterinary vaccines. [ABSTRACT FROM AUTHOR]

Published
2025
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11. Adiposity and risk of decline in glomerular filtration rate : Meta-analysis of individual participant data in a global consortium

Author

Chang AR, Grams ME, Ballew SH, Bilo H, Correa A, Evans M, Gutierrez OM, Hosseinpanah F, Iseki K, Kenealy T, Klein B, Kronenberg F, Lee BJ, Li Y, Miura K, Navaneethan SD, Roderick PJ, Valdivielso JM, Visseren FLJ, Zhang L, Gansevoort RT, Hallan SI, Levey AS, Matsushita K, Shalev V, Woodward M, Astor B, Appel L, Greene T, Chen T, Chalmers J, Arima H, Perkovic V, Yatsuya H, Tamakoshi K, Hirakawa Y, Coresh J, Sang Y, Polkinghorne K, Chadban S, Atkins R, Levin A, Djurdjev O, Klein R, Lee K, Liu L, Zhao M, Wang F, Wang J, Tang M, Heine G, Emrich I, Zawada A, Bauer L, Nally J, Schold J, Shlipak M, Sarnak M, Katz R, Hiramoto J, Iso H, Yamagishi K, Umesawa M, Muraki I, Fukagawa M, Maruyama S, Hamano T, Hasegawa T, Fujii N, Jafar T, Hatcher J, Poulter N, Chaturvedi N, Wheeler D, Emberson J, Townend J, Landray M, Brenner H, Schöttker B, Saum KU, Rothenbacher D, Fox C, Hwang SJ, Köttgen A, Schneider MP, Eckardt KU, Green J, Kirchner HL, Ito S, Miyazaki M, Nakayama M, Yamada G, Cirillo M, Romundstad S, Øvrehus M, Langlo KA, Irie F, Sairenchi T, Rebholz CM, Young B, Boulware LE, Ishikawa S, Yano Y, Kotani K, Nakamura T, Jee SH, Kimm H, Mok Y, Chodick G, Wetzels JFM, Blankestijn PJ, van Zuilen AD, Bots M, Inker L, Peralta C, Kollerits B, Ritz E, Nitsch D, Fletcher A, Bottinger E, Nadkarni GN, Ellis SB, Nadukuru R, Fernandez E, Betriu A, Bermudez-Lopez M, Stengel B, Metzger M, Flamant M, Houillier P, Haymann JP, Froissart M, Ueshima H, Okayama A, Tanaka S, Okamura T, Elley CR, Collins JF, Drury PL, Ohkubo T, Asayama K, Metoki H, Kikuya M, Iseki C, Nelson RG, Knowler WC, Bakker SJL, Heerspink HJL, Brunskill N, Major R, Shepherd D, Medcalf J, Jassal SK, Bergstrom J, Ix JH, Barrett-Connor E, Kovesdy C, Kalantar-Zadeh K, Sumida K, Muntner P, Warnock D, Judd S, Panwar B, de Zeeuw D, Brenner B, Sedaghat S, Ikram MA, Hoorn EJ, Dehghan A, Wong TY, Sabanayagam C, Cheng CY, Banu R, Segelmark M, Stendahl M, Schön S, Tangri N, Sud M, Naimark D, Wen CP, Tsao CK, Tsai MK, Chen CH, Konta T, Hirayama A, Ichikawa K, Hadaegh F, Mirbolouk M, Azizi F, Solbu MD, Jenssen TG, Eriksen BO, Eggen AE, Lannfelt L, Larsson A, Ärnlöv J, Landman GWD, van Hateren KJJ, Kleefstra N, Chen J, Kwak L, Surapaneni A., Chang, Ar, Grams, Me, Ballew, Sh, Bilo, H, Correa, A, Evans, M, Gutierrez, Om, Hosseinpanah F, Iseki K, Kenealy, T, Klein, B, Kronenberg, F, Lee, Bj, Li, Y, Miura, K, Navaneethan, Sd, Roderick, Pj, Valdivielso, Jm, Visseren, Flj, Zhang, L, Gansevoort, Rt, Hallan, Si, Levey, A, Matsushita, K, Shalev, V, Woodward, M, Astor, B, Appel, L, Greene, T, Chen, T, Chalmers, J, Arima, H, Perkovic, V, Yatsuya, H, Tamakoshi, K, Hirakawa, Y, Coresh, J, Sang, Y, Polkinghorne, K, Chadban, S, Atkins, R, Levin, A, Djurdjev, O, Klein, R, Lee, K, Liu, L, Zhao, M, Wang, F, Wang, J, Tang, M, Heine, G, Emrich, I, Zawada, A, Bauer, L, Nally, J, Schold, J, Shlipak, M, Sarnak, M, Katz, R, Hiramoto, J, Iso, H, Yamagishi, K, Umesawa, M, Muraki, I, Fukagawa, M, Maruyama, S, Hamano, T, Hasegawa, T, Fujii, N, Jafar, T, Hatcher, J, Poulter, N, Chaturvedi, N, Wheeler, D, Emberson, J, Townend, J, Landray, M, Brenner, H, Schöttker, B, Saum, Ku, Rothenbacher, D, Fox, C, Hwang, Sj, Köttgen, A, Schneider, Mp, Eckardt, Ku, Green, J, Kirchner, Hl, Ito, S, Miyazaki, M, Nakayama, M, Yamada, G, Cirillo, M, Romundstad, S, Øvrehus, M, Langlo, Ka, Irie, F, Sairenchi, T, Rebholz, Cm, Young, B, Boulware, Le, Ishikawa, S, Yano, Y, Kotani, K, Nakamura, T, Jee, Sh, Kimm, H, Mok, Y, Chodick, G, Wetzels, Jfm, Blankestijn, Pj, van Zuilen, Ad, Bots, M, Inker, L, Peralta, C, Kollerits, B, Ritz, E, Nitsch, D, Fletcher, A, Bottinger, E, Nadkarni, Gn, Ellis, Sb, Nadukuru, R, Fernandez, E, Betriu, A, Bermudez-Lopez, M, Stengel, B, Metzger, M, Flamant, M, Houillier, P, Haymann, Jp, Froissart, M, Ueshima, H, Okayama, A, Tanaka, S, Okamura, T, Elley, Cr, Collins, Jf, Drury, Pl, Ohkubo, T, Asayama, K, Metoki, H, Kikuya, M, Iseki, C, Nelson, Rg, Knowler, Wc, Bakker, Sjl, Heerspink, Hjl, Brunskill, N, Major, R, Shepherd, D, Medcalf, J, Jassal, Sk, Bergstrom, J, Ix, Jh, Barrett-Connor, E, Kovesdy, C, Kalantar-Zadeh, K, Sumida, K, Muntner, P, Warnock, D, Judd, S, Panwar, B, de Zeeuw, D, Brenner, B, Sedaghat, S, Ikram, Ma, Hoorn, Ej, Dehghan, A, Wong, Ty, Sabanayagam, C, Cheng, Cy, Banu, R, Segelmark, M, Stendahl, M, Schön, S, Tangri, N, Sud, M, Naimark, D, Wen, Cp, Tsao, Ck, Tsai, Mk, Chen, Ch, Konta, T, Hirayama, A, Ichikawa, K, Hadaegh, F, Mirbolouk, M, Azizi, F, Solbu, Md, Jenssen, Tg, Eriksen, Bo, Eggen, Ae, Lannfelt, L, Larsson, A, Ärnlöv, J, Landman, Gwd, van Hateren, Kjj, Kleefstra, N, Chen, J, Kwak, L, Surapaneni, A., Lifestyle Medicine (LM), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Asayama, Kei, and Sedaghat, SeyyedMah

Subjects
CHRONIC KIDNEY-DISEASE, Male, 030232 urology & nephrology, 030204 cardiovascular system & hematology, OBESITY PARADOX, Body Mass Index, BMI, eGFR, CKD-PC, Cohort Studies, 0302 clinical medicine, Risk Factors, Urologi och njurmedicin, Medicine, ALL-CAUSE MORTALITY, Adiposity, 2. Zero hunger, Aged, 80 and over, Medicine(all), education.field_of_study, Hazard ratio, ASSOCIATION, General Medicine, Middle Aged, 3. Good health, Cohort, Female, Waist Circumference, Life Sciences & Biomedicine, WAIST CIRCUMFERENCE, Obesity paradox, Glomerular Filtration Rate, Adult, Waist, Population, Renal function, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, CKD, Urology and Nephrology, Humans, Mortality, education, Aged, Science & Technology, business.industry, Research, medicine.disease, Body Height, BODY-MASS INDEX, Kidney Failure, Chronic, WEIGHT, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Body mass index, Demography, Kidney disease
Abstract

ObjectiveTo evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.DesignIndividual participant data meta-analysis.SettingCohorts from 40 countries with data collected between 1970 and 2017.ParticipantsAdults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).Main outcome measuresGFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR 2) and all cause mortality.ResultsOver a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.ConclusionsElevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Published
2019

15. Using Twine Open-Source Software to Create Serious and Entertaining Digital Games - Enhancing Doctor and Patient Management of Diabetes

Author

Quaill, N., Lai, M., Oje, M., Linn, A., Rea, P., Livingstone, D., Nally, J., and Boyle, J.

Subjects
education
Abstract

Background: Diabetes management is a complex learning process for patients and an area of low confidence amongst junior doctors. Serious digital games allow healthcare professionals to simulate clinical interactions in a safe environment. Many facets of diabetes management, such as carbohydrate counting, also lend themselves to gamification. Our work utilises Twine open-source software to create digital games that facilitate patient and healthcare professional education in diabetes management.\ud \ud Method: Three serious digital games with virtual patients were developed using Twine open-source software, Wacom Intuous Pro, Autodesk SketchBook, Camtasia Studio, and simulated patient videos. Chalk-talk explanations of key concepts are integrated into these cases. A prototype was piloted by a small cohort of medical students and junior doctors and evaluated using the Kirkpatrick model. A detective-themed game was also developed using the aforementioned technology to enable diabetic patients to engage in aspects of management in a safe environment.\ud \ud Results: Pilots with senior medical students and junior doctors have demonstrated high levels of engagement, as well as significant improvements in confidence and knowledge (p

Published
2019

18. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies.

Author

Ichikawa K., Collins J.F., Drury P.L., Ellis S.G., Nadukuru R., Metzger M., Flamant M., Houillier P., Haymann J.-P., Froissart M., Kenealy T., Elley R.C., Cuddeback J.K., Ciemins E.L., Stempniewicz R., Nelson R.G., Knowler W.C., Bakker S.J., Major R.W., Medcalf J.F., Shepherd D., Barrett-Connor E., Bergstrom J., Ix J.H., Molnar M.Z., Maciulaitis R., Manley T., Smith K., Stockbridge N., Thompson A., Vetter T., Willis K., Zhang L., Coresh J., Heerspink H.J.L., Sang Y., Matsushita K., Arnlov J., Astor B.C., Black C., Brunskill N.J., Carrero J.-J., Feldman H.I., Fox C.S., Inker L.A., Ishani A., Ito S., Jassal S., Konta T., Polkinghorne K., Romundstad S., Solbu M.D., Stempniewicz N., Stengel B., Tonelli M., Umesawa M., Waikar S.S., Wen C.-P., Wetzels J.F.M., Woodward M., Grams M.E., Kovesdy C.P., Levey A.S., Gansevoort R.T., Appel L.J., Greene T., Chen T.K., Chalmers J., Arima H., Perkovic V., Levin A., Djurdjev O., Tang M., Nally J., Navaneethan S.D., Schold J.D., Weldegiorgis M., Herrington W.G., Smith M., Hsu C.Y., Hwang S.-J., Chang A.R., Kirchner H.L., Green J.A., Ho K., Marks A., Prescott G., Clark L.E., Fluck N., Shalev V., Chodick G., Blankestijn P.J., Van Zuilen A., Van den Brand J.A., Sarnak M.J., Bottinger E., Nadkarni G.N., Sumida K., de Zeeuw D., Brenner B., Qureshi A.R., Elinder C.-G., Runesson B., Evans M., Segelmark M., Stendahl M., Schon S., Naimark D.M., Tangri N., Sud M., Hirayama A., Bilo H.J., Landman G.W., Van Hateren K.J., Kleefstra N., Hallan S.I., Ballew S.H., Chen J., Kwak L., Surapaneni A., Parving H.-H., Rodby R.A., Rohde R.D., Lewis J.B., Lewis E., Perrone R.D., Abebe K.Z., Hou F.F., Xie D., Hunsicker L.G., Imai E., Kobayashi F., Makino H., Remuzzi G., Ruggenenti P., Eckardt K.-U., Gudmundsdottir H., Ichikawa K., Collins J.F., Drury P.L., Ellis S.G., Nadukuru R., Metzger M., Flamant M., Houillier P., Haymann J.-P., Froissart M., Kenealy T., Elley R.C., Cuddeback J.K., Ciemins E.L., Stempniewicz R., Nelson R.G., Knowler W.C., Bakker S.J., Major R.W., Medcalf J.F., Shepherd D., Barrett-Connor E., Bergstrom J., Ix J.H., Molnar M.Z., Maciulaitis R., Manley T., Smith K., Stockbridge N., Thompson A., Vetter T., Willis K., Zhang L., Coresh J., Heerspink H.J.L., Sang Y., Matsushita K., Arnlov J., Astor B.C., Black C., Brunskill N.J., Carrero J.-J., Feldman H.I., Fox C.S., Inker L.A., Ishani A., Ito S., Jassal S., Konta T., Polkinghorne K., Romundstad S., Solbu M.D., Stempniewicz N., Stengel B., Tonelli M., Umesawa M., Waikar S.S., Wen C.-P., Wetzels J.F.M., Woodward M., Grams M.E., Kovesdy C.P., Levey A.S., Gansevoort R.T., Appel L.J., Greene T., Chen T.K., Chalmers J., Arima H., Perkovic V., Levin A., Djurdjev O., Tang M., Nally J., Navaneethan S.D., Schold J.D., Weldegiorgis M., Herrington W.G., Smith M., Hsu C.Y., Hwang S.-J., Chang A.R., Kirchner H.L., Green J.A., Ho K., Marks A., Prescott G., Clark L.E., Fluck N., Shalev V., Chodick G., Blankestijn P.J., Van Zuilen A., Van den Brand J.A., Sarnak M.J., Bottinger E., Nadkarni G.N., Sumida K., de Zeeuw D., Brenner B., Qureshi A.R., Elinder C.-G., Runesson B., Evans M., Segelmark M., Stendahl M., Schon S., Naimark D.M., Tangri N., Sud M., Hirayama A., Bilo H.J., Landman G.W., Van Hateren K.J., Kleefstra N., Hallan S.I., Ballew S.H., Chen J., Kwak L., Surapaneni A., Parving H.-H., Rodby R.A., Rohde R.D., Lewis J.B., Lewis E., Perrone R.D., Abebe K.Z., Hou F.F., Xie D., Hunsicker L.G., Imai E., Kobayashi F., Makino H., Remuzzi G., Ruggenenti P., Eckardt K.-U., and Gudmundsdottir H.

Abstract

Background: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Method(s): In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Finding(s): Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the C

Published
2019

19. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies

Author

Coresh, J, Heerspink, HJL, Sang, Y, Matsushita, K, Arnlov, J, Astor, BC, Black, C, Brunskill, NJ, Carrero, JJ, Feldman, HI, Fox, CS, Inker, LA, Ishani, A, Ito, S, Jassal, S, Konta, T, Polkinghorne, K, Romundstad, S, Solbu, MD, Stempniewicz, N, Stengel, B, Tonelli, M, Umesawa, M, Waikar, SS, Wen, CP, Wetzels, JFM, Woodward, M, Grams, ME, Kovesdy, CP, Levey, AS, Gansevoort, RT, Appel, LJ, Greene, T, Chen, TK, Chalmers, J, Arima, H, Perkovic, V, Levin, A, Djurdjev, O, Tang, M, Nally, J, Navaneethan, SD, Schold, JD, Weldegiorgis, M, Herrington, WG, Smith, M, Hsu, CY, Hwang, SJ, Chang, AR, Kirchner, HL, Green, JA, Ho, K, Marks, A, Prescott, G, Clark, LE, Fluck, N, Shalev, V, Chodick, G, Blankestijn, PJ, Van Zuilen, A, Van den Brand, JA, Sarnak, MJ, Bottinger, E, Nadkarni, GN, Ellis, SG, Nadukuru, R, Metzger, M, Flamant, M, Houillier, P, Haymann, JP, Froissart, M, Kenealy, T, Elley, RC, Collins, JF, Drury, PL, Cuddeback, JK, Ciemins, EL, Stempniewicz, R, Nelson, RG, Knowler, WC, Bakker, SJ, Major, RW, Medcalf, JF, Shepherd, D, Barrett-Connor, E, Bergstrom, J, Ix, JH, Molnar, MZ, Sumida, K, de Zeeuw, D, Brenner, B, Qureshi, AR, Elinder, CG, Runesson, B, Evans, M, Segelmark, M, Stendahl, M, Schön, S, Naimark, DM, Tangri, N, Coresh, J, Heerspink, HJL, Sang, Y, Matsushita, K, Arnlov, J, Astor, BC, Black, C, Brunskill, NJ, Carrero, JJ, Feldman, HI, Fox, CS, Inker, LA, Ishani, A, Ito, S, Jassal, S, Konta, T, Polkinghorne, K, Romundstad, S, Solbu, MD, Stempniewicz, N, Stengel, B, Tonelli, M, Umesawa, M, Waikar, SS, Wen, CP, Wetzels, JFM, Woodward, M, Grams, ME, Kovesdy, CP, Levey, AS, Gansevoort, RT, Appel, LJ, Greene, T, Chen, TK, Chalmers, J, Arima, H, Perkovic, V, Levin, A, Djurdjev, O, Tang, M, Nally, J, Navaneethan, SD, Schold, JD, Weldegiorgis, M, Herrington, WG, Smith, M, Hsu, CY, Hwang, SJ, Chang, AR, Kirchner, HL, Green, JA, Ho, K, Marks, A, Prescott, G, Clark, LE, Fluck, N, Shalev, V, Chodick, G, Blankestijn, PJ, Van Zuilen, A, Van den Brand, JA, Sarnak, MJ, Bottinger, E, Nadkarni, GN, Ellis, SG, Nadukuru, R, Metzger, M, Flamant, M, Houillier, P, Haymann, JP, Froissart, M, Kenealy, T, Elley, RC, Collins, JF, Drury, PL, Cuddeback, JK, Ciemins, EL, Stempniewicz, R, Nelson, RG, Knowler, WC, Bakker, SJ, Major, RW, Medcalf, JF, Shepherd, D, Barrett-Connor, E, Bergstrom, J, Ix, JH, Molnar, MZ, Sumida, K, de Zeeuw, D, Brenner, B, Qureshi, AR, Elinder, CG, Runesson, B, Evans, M, Segelmark, M, Stendahl, M, Schön, S, Naimark, DM, and Tangri, N

Abstract

Background: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Methods: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Findings: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-P

Published
2019

22. Past Decline Versus Current eGFR and Subsequent Mortality Risk

Author

Naimark DMJ, Grams ME, Matsushita K, Black C, Drion I, Fox CS, Inker LA, Ishani A, Jee SA, Kitamura A, Lea JP, Nally J, Peralta CA, Rothenbacher D, Ryu S, Tonelli M, Yatsuya H, Coresh J, Gansevoort RT, Warnock DG, Woodward M, de Jong PE, the CKD Prognosis Consortium, Wright JTJr, Appel LJ, Greene T, MacMahon S, Chalmers J, Arima H, Yamashita K, Toyoshima H, Tamakoshi K, Hemmelgarn B, James M, Sang Y, Atkins RC, Polkinghorne KR, Chadban S, Shankar A, Klein R, Klein BEK, Lee KE, Levin A, Djurdjev O, Sacks FM, Curhan GC, Zawada AM, Rogacev KS, Seiler S, Heine GH, Navaneethan SD, Schold JD, Shlipak M, Sarnak MJ, Katz R, Imano H, Yamagishi K, Wheeler DC, Emberson J, Townend JN, Landray MJ, Brenner H, Müller H, Schöttker B, Hwang S-J, Meigs JB, Uphadhay A, Green J, Kirchner HL, Perkins R, Chang AR, Fluck N, Prescott GJ, Cirillo M, Hallan S, Aasarød K, Øien CM, Radtke M, Irie F, Iso H, Sairenchi T, Smith DH, Thorp ML, Johnson ES, Lee BJ, Guallar E, Chang SY, Cho J, Shin H, Chodick G, Shalev V, Birnbaum YC, Shainberg B, Wetzels JFM, Blankestijn PJ, van Zuilen AD, Levey AS, Neaton JD, Froissart M, Stengel B, Metzger M, Haymann J-P, Houillier P, Flamant M, Elley CR, Kenealy T, Moyes SA, Collins JF, Drury PL, Ohkubo T, Metoki H, Nakayama M, Imai Y, Iseki K, Nelson RG, Knowler WC, Bakker SJL, LHillege H, Jassal SK, Bergstrom J, Ix JH, Barrett-Connor E, Heerspink HJL, Brenner BE, de Zeeuw D, Kimm H, Mok Y, Tangri N, Wen C-P, Wen S-F, Tsao C-K, Tsai M-K, Ärnlöv J, Lannfelt L, Larsson A, Kovesdy CP, Kalantar-Zadeh K, Bilo HJ, Kleefstra N, Groenier KH, Joosten H, Ballew SH, Naimark, Dmj, Grams, Me, Matsushita, K, Black, C, Drion, I, Fox, C, Inker, La, Ishani, A, Jee, Sa, Kitamura, A, Lea, Jp, Nally, J, Peralta, Ca, Rothenbacher, D, Ryu, S, Tonelli, M, Yatsuya, H, Coresh, J, Gansevoort, Rt, Warnock, Dg, Woodward, M, de Jong, Pe, the CKD Prognosis, Consortium, Wright, Jtjr, Appel, Lj, Greene, T, Macmahon, S, Chalmers, J, Arima, H, Yamashita, K, Toyoshima, H, Tamakoshi, K, Hemmelgarn, B, James, M, Sang, Y, Atkins, Rc, Polkinghorne, Kr, Chadban, S, Shankar, A, Klein, R, Klein, Bek, Lee, Ke, Levin, A, Djurdjev, O, Sacks, Fm, Curhan, Gc, Zawada, Am, Rogacev, K, Seiler, S, Heine, Gh, Navaneethan, Sd, Schold, Jd, Shlipak, M, Sarnak, Mj, Katz, R, Imano, H, Yamagishi, K, Wheeler, Dc, Emberson, J, Townend, Jn, Landray, Mj, Brenner, H, Müller, H, Schöttker, B, Hwang, S-J, Meigs, Jb, Uphadhay, A, Green, J, Kirchner, Hl, Perkins, R, Chang, Ar, Fluck, N, Prescott, Gj, Cirillo, M, Hallan, S, Aasarød, K, Øien, Cm, Radtke, M, Irie, F, Iso, H, Sairenchi, T, Smith, Dh, Thorp, Ml, Johnson, E, Lee, Bj, Guallar, E, Chang, Sy, Cho, J, Shin, H, Chodick, G, Shalev, V, Birnbaum, Yc, Shainberg, B, Wetzels, Jfm, Blankestijn, Pj, van Zuilen, Ad, Levey, A, Neaton, Jd, Froissart, M, Stengel, B, Metzger, M, Haymann, J-P, Houillier, P, Flamant, M, Elley, Cr, Kenealy, T, Moyes, Sa, Collins, Jf, Drury, Pl, Ohkubo, T, Metoki, H, Nakayama, M, Imai, Y, Iseki, K, Nelson, Rg, Knowler, Wc, Bakker, Sjl, Lhillege, H, Jassal, Sk, Bergstrom, J, Ix, Jh, Barrett-Connor, E, Heerspink, Hjl, Brenner, Be, de Zeeuw, D, Kimm, H, Mok, Y, Tangri, N, Wen, C-P, Wen, S-F, Tsao, C-K, Tsai, M-K, Ärnlöv, J, Lannfelt, L, Larsson, A, Kovesdy, Cp, Kalantar-Zadeh, K, Bilo, Hj, Kleefstra, N, Groenier, Kh, Joosten, H, Ballew, Sh, Cardiovascular Centre (CVC), and Groningen Kidney Center (GKC)

Subjects
Gerontology, Male, CHRONIC KIDNEY-DISEASE, medicine.medical_specialty, Time Factors, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, ALL-CAUSE, GLOMERULAR-FILTRATION-RATE, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Cause of Death, Epidemiology, Risk of mortality, medicine, EQUATION, Humans, Clinical Epidemiology, Renal Insufficiency, Chronic, Aged, Proportional Hazards Models, business.industry, Hazard ratio, STAGE RENAL-DISEASE, DEATH, General Medicine, Middle Aged, POPULATION COHORTS, Confidence interval, Increased risk, Nephrology, CARDIOVASCULAR-DISEASE, COLLABORATIVE METAANALYSIS, Female, business, HIGHER ALBUMINURIA, All cause mortality, Glomerular Filtration Rate
Abstract

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

Published
2016

24. Animal board invited review: advances in proteomics for animal and food sciences

Author

Almeida, A. M., Bassols, A., Bendixen, E., Bhide, M., Ceciliani, F., Cristobal, S., Eckersall, P. D., Hollung, K., Lisacek, F., Mazzucchelli, G., McLaughlin, M., Miller, I., Nally, J. E., Plowman, J., Renaut, J., Rodrigues, P., Roncada, P., Staric, J., Turk, R., Almeida, A. M., Bassols, A., Bendixen, E., Bhide, M., Ceciliani, F., Cristobal, S., Eckersall, P. D., Hollung, K., Lisacek, F., Mazzucchelli, G., McLaughlin, M., Miller, I., Nally, J. E., Plowman, J., Renaut, J., Rodrigues, P., Roncada, P., Staric, J., and Turk, R.

Abstract

Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps ex

Published
2017

26. Animal board invited review: advances in proteomics for animal and food sciences

Author

Almeida, A. M., Bassols, A., Bendixen, E., Bhide, M., Ceciliani, F., Cristobal, Susana, Eckersall, P. D., Hollung, K., Lisacek, F., Mazzucchelli, G., McLaughlin, M., Miller, I., Nally, J. E., Plowman, J., Renaut, J., Rodrigues, P., Roncada, P., Staric, J., Turk, R., Almeida, A. M., Bassols, A., Bendixen, E., Bhide, M., Ceciliani, F., Cristobal, Susana, Eckersall, P. D., Hollung, K., Lisacek, F., Mazzucchelli, G., McLaughlin, M., Miller, I., Nally, J. E., Plowman, J., Renaut, J., Rodrigues, P., Roncada, P., Staric, J., and Turk, R.

Abstract

Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps ex, Funding Agencies|European Science Foundation (Brussels, Belgium)

Published
2015
Full Text
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28. Molecular analysis of the Enterobacter sakazakii O-antigen gene locus

Author

Mullane, N R, O'Gaora, P, Nally, J E, Iversen, C, Whyte, P, Wall, P G, Fannning, S, and University of Zurich

Subjects
1305 Biotechnology, 570 Life sciences, biology, 2402 Applied Microbiology and Biotechnology, 610 Medicine & health, 2303 Ecology, 10082 Institute of Food Safety and Hygiene, 1106 Food Science
Published
2008

30. Procedure guideline for diagnosis of renovascular hypertension

Author

Taylor A T, Jr, Fletcher, J. W., Nally J V, Jr, MDonald Blaufox, Dubovsky, E. V., Fine, E. J., Kahn, D., Morton, K. A., Russell, C. D., Sfakianakis, G. N., Aurell, M., Dondi, M., Fommei, E., Geyskes, G., Granerus, G., Oei, H. -Y, and Radiology & Nuclear Medicine

Published
1998

38. Identification of Immunologically Relevant Proteins of Chlamydophila abortus Using Sera from Experimentally Infected Pregnant Ewes

Author

Marques, P. X., primary, Souda, Puneet, additional, O'Donovan, J., additional, Gutierrez, J., additional, Williams, E. J., additional, Worrall, S., additional, McElroy, M., additional, Proctor, A., additional, Brady, C., additional, Sammin, D., additional, Basset, H. F., additional, Whitelegge, Julian P., additional, Markey, B. E., additional, and Nally, J. E., additional

Published
2010
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