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127 results on '"Taddei, T."'

1. Impact of physical model error on State Estimation for neutronics applications

Author

Taumhas, Y. Conjungo, Labeurthre, D., Madiot, F., Mula, O., and Taddei, T.

Subjects
Mathematics - Numerical Analysis
Abstract

In this paper, we consider the inverse problem of state estimation of nuclear power fields in a power plant from a limited number of observations of the neutron flux. For this, we use the Parametrized Background Data Weak approach. The method combines the observations with a parametrized PDE model for the behavior of the neutron flux. Since, in general, even the most sophisticated models cannot perfectly capture reality, an inevitable model error is made. We investigate the impact of the model error in the power reconstruction when we use a diffusion model for the neutron flux, and assume that the true physics are governed by a neutron transport model., Comment: arXiv admin note: text overlap with arXiv:2106.09421

Published
2022

4. Author Correction: Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s disease (Nature Communications, (2021), 12, 1, (721), 10.1038/s41467-021-21057-y)

Author

Roe, JM, Vidal-Piñeiro, D, Sørensen, Ø, Brandmaier, AM, Düzel, S, Gonzalez, HA, Kievit, RA, Knights, E, Kühn, S, Lindenberger, U, Mowinckel, AM, Nyberg, L, Park, DC, Pudas, S, Rundle, MM, Walhovd, KB, Fjell, AM, Westerhausen, R, Masters, CL, Bush, AI, Fowler, C, Darby, D, Pertile, K, Restrepo, C, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Collins, S, Thai, C, Trounson, B, Lennon, K, Li, QX, Ugarte, FY, Volitakis, I, Vovos, M, Williams, R, Baker, J, Russell, A, Peretti, M, Milicic, L, Lim, L, Rodrigues, M, Taddei, K, Taddei, T, Hone, E, Lim, F, Fernandez, S, Rainey-Smith, S, Pedrini, S, Martins, R, Doecke, J, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, Hanson, D, Dore, V, Zhang, P, Burnham, S, Rowe, CC, Villemagne, VL, Yates, P, Pejoska, SB, Jones, G, Ames, D, Cyarto, E, Lautenschlager, N, Barnham, K, Cheng, L, Hill, A, Killeen, N, Maruff, P, Silbert, B, Brown, B, Sohrabi, H, Savage, G, Vacher, M, Roe, JM, Vidal-Piñeiro, D, Sørensen, Ø, Brandmaier, AM, Düzel, S, Gonzalez, HA, Kievit, RA, Knights, E, Kühn, S, Lindenberger, U, Mowinckel, AM, Nyberg, L, Park, DC, Pudas, S, Rundle, MM, Walhovd, KB, Fjell, AM, Westerhausen, R, Masters, CL, Bush, AI, Fowler, C, Darby, D, Pertile, K, Restrepo, C, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Collins, S, Thai, C, Trounson, B, Lennon, K, Li, QX, Ugarte, FY, Volitakis, I, Vovos, M, Williams, R, Baker, J, Russell, A, Peretti, M, Milicic, L, Lim, L, Rodrigues, M, Taddei, K, Taddei, T, Hone, E, Lim, F, Fernandez, S, Rainey-Smith, S, Pedrini, S, Martins, R, Doecke, J, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, Hanson, D, Dore, V, Zhang, P, Burnham, S, Rowe, CC, Villemagne, VL, Yates, P, Pejoska, SB, Jones, G, Ames, D, Cyarto, E, Lautenschlager, N, Barnham, K, Cheng, L, Hill, A, Killeen, N, Maruff, P, Silbert, B, Brown, B, Sohrabi, H, Savage, G, and Vacher, M

Abstract

In this article the affiliation details for Ulman Lindenberger were incorrectly given as ‘Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany’ but should have been ‘Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany’, ‘Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany’. The original article has been corrected.

Published
2022

6. Fifteen years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and observations from 2,359 older adults spanning the spectrum from cognitive normality to Alzheimer’s Disease

Author

Fowler, C., Rainey-Smith, S.R., Bird, S., Bomke, J., Bourgeat, P., Brown, B.M., Burnham, S.C., Bush, A.I., Chadunow, C., Collins, S., Doecke, J., Doré, V., Ellis, K.A., Evered, L., Fazlollahi, A., Fripp, J., Gardener, S.L., Gibson, S., Grenfell, R., Harrison, E., Head, R., Jin, L., Kamer, A., Lamb, F., Lautenschlager, N.T., Laws, S.M., Li, Q-X, Lim, L., Lim, Y.Y., Louey, A., Macaulay, S.L., Mackintosh, L., Martins, R.N., Maruff, P., Masters, C.L., McBride, S., Milicic, L., Peretti, M., Pertile, K., Porter, T., Radler, M., Rembach, A., Robertson, J., Rodrigues, M., Rowe, C.C., Rumble, R., Salvado, O., Savage, G., Silbert, B., Soh, M., Sohrabi, H.R., Taddei, K., Taddei, T., Thai, C., Trounson, B., Tyrrell, R., Vacher, M., Varghese, S., Villemagne, V.L., Weinborn, M., Woodward, M., Xia, Y., Ames, D., Fowler, C., Rainey-Smith, S.R., Bird, S., Bomke, J., Bourgeat, P., Brown, B.M., Burnham, S.C., Bush, A.I., Chadunow, C., Collins, S., Doecke, J., Doré, V., Ellis, K.A., Evered, L., Fazlollahi, A., Fripp, J., Gardener, S.L., Gibson, S., Grenfell, R., Harrison, E., Head, R., Jin, L., Kamer, A., Lamb, F., Lautenschlager, N.T., Laws, S.M., Li, Q-X, Lim, L., Lim, Y.Y., Louey, A., Macaulay, S.L., Mackintosh, L., Martins, R.N., Maruff, P., Masters, C.L., McBride, S., Milicic, L., Peretti, M., Pertile, K., Porter, T., Radler, M., Rembach, A., Robertson, J., Rodrigues, M., Rowe, C.C., Rumble, R., Salvado, O., Savage, G., Silbert, B., Soh, M., Sohrabi, H.R., Taddei, K., Taddei, T., Thai, C., Trounson, B., Tyrrell, R., Vacher, M., Varghese, S., Villemagne, V.L., Weinborn, M., Woodward, M., Xia, Y., and Ames, D.

Abstract

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Published
2021

7. Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

Author

Zhang, Q, Sidorenko, J, Couvy-Duchesne, B, Marioni, RE, Wright, MJ, Goate, AM, Marcora, E, Huang, KL, Porter, T, Laws, SM, Masters, CL, Bush, AI, Fowler, C, Darby, D, Pertile, K, Restrepo, C, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Collins, S, Thai, C, Trounson, B, Lennon, K, Li, QX, Ugarte, FY, Volitakis, I, Vovos, M, Williams, R, Baker, J, Russell, A, Peretti, M, Milicic, L, Lim, L, Rodrigues, M, Taddei, K, Taddei, T, Hone, E, Lim, F, Fernandez, S, Rainey-Smith, S, Pedrini, S, Martins, R, Doecke, J, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, Hanson, D, Dore, V, Zhang, P, Burnham, S, Rowe, CC, Villemagne, VL, Yates, P, Pejoska, SB, Jones, G, Ames, D, Cyarto, E, Lautenschlager, N, Barnham, K, Cheng, L, Hill, A, Killeen, N, Maruff, P, Silbert, B, Brown, B, Sohrabi, H, Savage, G, Vacher, M, Sachdev, PS, Mather, KA, Armstrong, NJ, Thalamuthu, A, Brodaty, H, Yengo, L, Yang, J, Wray, NR, McRae, AF, Visscher, PM, Zhang, Q, Sidorenko, J, Couvy-Duchesne, B, Marioni, RE, Wright, MJ, Goate, AM, Marcora, E, Huang, KL, Porter, T, Laws, SM, Masters, CL, Bush, AI, Fowler, C, Darby, D, Pertile, K, Restrepo, C, Roberts, B, Robertson, J, Rumble, R, Ryan, T, Collins, S, Thai, C, Trounson, B, Lennon, K, Li, QX, Ugarte, FY, Volitakis, I, Vovos, M, Williams, R, Baker, J, Russell, A, Peretti, M, Milicic, L, Lim, L, Rodrigues, M, Taddei, K, Taddei, T, Hone, E, Lim, F, Fernandez, S, Rainey-Smith, S, Pedrini, S, Martins, R, Doecke, J, Bourgeat, P, Fripp, J, Gibson, S, Leroux, H, Hanson, D, Dore, V, Zhang, P, Burnham, S, Rowe, CC, Villemagne, VL, Yates, P, Pejoska, SB, Jones, G, Ames, D, Cyarto, E, Lautenschlager, N, Barnham, K, Cheng, L, Hill, A, Killeen, N, Maruff, P, Silbert, B, Brown, B, Sohrabi, H, Savage, G, Vacher, M, Sachdev, PS, Mather, KA, Armstrong, NJ, Thalamuthu, A, Brodaty, H, Yengo, L, Yang, J, Wray, NR, McRae, AF, and Visscher, PM

Abstract

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.

Published
2020

9. Prognostic significance of serum uric acid in outpatients with chronic heart failure is complex and related to body mass index: Data from the IN-CHF Registry

Author

Baldasseroni, S, Urso, R, Maggioni, Ap, Orso, F, Fabbri, G, Marchionni, N, Tavazzi, L, the IN CHF Investigators: Mezzani, A, Bielli, M, Milanese, G, Ugliengo, G, Pozzi, R, Rabajoli, F, Bosimini, E, Begliuomini, G, Ferrari, A, Barzizza, F, Valsecchi, F, Dadda, F, Faggiano, P, Castiglioni, G, Gibelli, G, Turelli, Al, Belluschi, R, Bianchi, C, Emanuelli, C, Gramenzi, S, Foti, S, Agnelli, D, Mascioli, G, Cazzani, E, Zanelli, E, Domenighini, D, Castelli, C, Moroni, E, Gara, E, Guzzetti, S, Muzzupappa, S, Turiel, M, Cappiello, E, Sandrone, G, Recalcati, F, Valenti, D, Achilli, F, Vincenzi, A, Rusconi, F, Palvarini, M, Ghio, S, Fontana, A, Giusti, A, Scelsi, L, Sebastiani, R, Ceresa, M, Nassiacos, D, Meloni, S, Nicoli, T, Bandini, P, Pedretti, R, Paolucci, M, Amati, L, Ravetta, M, Morandi, F, Provasoli, S, Bertolini, A, Imperiale, D, Agen, W, Planca, E, Quorso, P, Ferro, A, Pedrolli, C, Russo, P, Tarantini, L, Candelpergher, G, Cannarozzo, Pp, De Cian, F, Agnoli, A, Stefanini, Mg, Cacciavillani, L, Boffa, Gm, Mario, L, Renosto, G, Stritoni, P, Varotto, L, Penzo, M, Perini, G, Giuliano, G, Barducci, E, Piazza, R, Albanese, Mc, Fresco, C, Picco, F, Venturini, P, Camerini, A, Griffo, R, Derchi, G, Delfino, L, Pizzorno, L, Mazzantini, S, Torre, F, Orlandi, S, Bertoli, D, Gentile, A, Naccarella, F, Gatti, M, Coluccini, M, Morgagni, G, Alfano, G, Reggianini, L, Sansoni, S, Serra, W, Passerini, F, Del Corso, P, Rusconi, L, Marzaloni, M, Mezzetti, M, Gambarati, Gp, Mariani, Pr, Volterrani, C, Venturi, F, Zambald, G, Casolo, G, Moschi, G, Geri Brandinelli, A, Miracapillo, G, Boni, A, Italiani, G, Vergoni, W, Paci, Am, Lattanzi, F, Reisenhofer, B, Severini, D, Taddei, T, Dalle Luche, A, Comella, A, Gasperini, U, Cocchieri, M, Alunni, G, Bosi, E, Panciarola, R, Maragoni, G, Bardelli, G, Testarmata, P, Pasetti, L, Budini, A, Gabrilelli, D, Coderoni, B, Midi, P, Romaniello, C, Del Sindaco, D, Leggio, F, Terranova, A, Pulignano, G, Pozzar, F, Ansalone, G, Magris, B, Giannantoni, P, Cacciatore, G, Bottero, G, Scaffidi, G, Valtorta, C, Salustri, A, Amadeo, F, Barbato, G, Aspromonte, N, Baldo, V, Baldo, E, Frattaroli, C, Mariani, A, Di Marco, G, Levantesi, G, Potena, Ap, Colonna, N, Montano, A, Sensale, P, Maiolica, O, Somelli, A, Napolitano, F, Provvisiero, P, Bottiglieri, P, Ciriello, N, Angelini, E, Andriulo, C, De Santis, F, Cocco, F, Zecca, A, Pennetta, A, Mariello, F, Magliari, F, De Giorgi, A, Callerame, M, Santoro, V, Pede, S, Renna, A, De Donno, O, De Lorenzi, E, Polimeni, G, Russo, Va, Mangia, R, Truncellito, L, Cariello, Fp, Affinita, M, Perticone, F, Cloro, C, Borelli, D, Matta, M, Lopresti, D, Misuraca, G, Caporale, R, Chiappetta, P, Tripodi, E, Tassone, F, Salituri, S, Errigo, C, Meringolo, G, Donnangelo, L, Canonico, G, Coco, R, Franco, M, Coglitore, A, Donato, A, Di Tano, G, Cento, Domenico, DE GREGORIO, Cesare, Mongiovı, M, Schillaci, Am, Mirto, Ij, Clemenza, F, Ingrillı, F, Cavallaro, A, Aloisi, B, Ledda, G, Rizzo, C, Porcu, M, Salis, S, Pistis, L, Pili, G, Piras, S, Maoddi, I, and Uras, F.

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Hyperuricemia, Models, Biological, Severity of Illness Index, Body Mass Index, chemistry.chemical_compound, Thinness, Internal medicine, Severity of illness, Ambulatory Care, Humans, Medicine, Registries, Mortality, Survival analysis, Aged, Retrospective Studies, Aged, 80 and over, Heart Failure, Nutrition and Dietetics, business.industry, Hazard ratio, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Confidence interval, Uric Acid, Surgery, Italy, chemistry, Heart failure, Cardiology, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract

In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF).All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⁻¹ vs 6.6 mg dl⁻¹, p0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⁻²) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⁻¹.Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state.

Published
2012

10. High content, multi-parameter analyses in buccal cells to identify Alzheimer's disease

Author

François, M., Fenech, M., Thomas, P., Hor, M., Rembach, A., Martins, R.N., Rainey-Smith, S.R., Masters, C.L., Ames, D., Rowe, C.C., Macaulay, S.L., Hill, A.F., Leifert, W.R., Appannah, A., Barnes, M., Barnham, K., Bedo, J., Bellingham, S., Bon, L., Bourgeat, P., Brown, B., Buckley, R., Burnham, S., Bush, A., Chandler, G., Chen, K., Clarnette, R., Collins, S., Cooke, I., Cowie, T., Cox, K., Cuningham, E., Cyarto, E., Dang, P.A.V., Darby, D., Desmond, P., Doecke, J., Dore, V., Downing, H., Dridan, B., Duesing, K., Fahey, M., Farrow, M., Faux, N., Fernandez, S., Fernando, B., Fowler, C., Fripp, J., Frost, S., Gardener, S., Gibson, S., Graham, P., Gupta, V., Hansen, D., Harrington, K., Hone, E., Horne, M., Huckstepp, B., Jones, A., Jones, G., Kamer, A., Kanagasingam, Y., Keam, L., Kowalczyk, A., Krivdic, B., Lam, C.P., Lamb, F., Lautenschlager, N., Laws, S., Lenzo, N., Leroux, H., Lftikhar, F., Li, Q-X, Lim, F., Lim, L., Lockett, L., Lucas, K., Mano, M., Marczak, C., Martins, G., Matsumoto, Y., Bird, S., McBride, S., McKay, R., Mulligan, R., Nash, T., Nigro, J., O'Keefe, G., Ong, K., Parker, B., Pedrini, S., Peiffer, J., Pejoska, S., Penny, L., Perez, K., Pertile, K., Phal, P., Porter, T., Raniga, P., Restrepo, C., Riley, M., Roberts, B., Robertson, J., Rodrigues, M., Rooney, A., Rumble, R., Ryan, T., Salvado, O., Samuel, M., Saunders, I., Savage, G., Silbert, B., Sohrabi, H.R., Syrette, J., Szoeke, C., Taddei, K., Taddei, T., Tan, S., Tegg, M., Trivedi, D., Trounson, B., Veljanovski, R., Verdile, G., Villemagne, V., Volitakis, I., Vockler, C., Vovos, M., Vrantsidis, F., Walker, S., Watt, A., Weinborn, M., Wilson, B., Woodward, M., Yastrubetskaya, O., Yates, P., Zhang, P., Chatterjee, P., Creegan, R., De Ruyck, K., Ding, H., Groth, D., Head, R., Krause, D., Lachovitzki, R., Lim, Y.Y., Lintern, T., Mondal, A., Nuttall, S., O'Callaghan, N., Osborne, L., Pang, C., Patten, G., Tuckfield, A., Varghese, J., Wilson, A., Zhang, Q., François, M., Fenech, M., Thomas, P., Hor, M., Rembach, A., Martins, R.N., Rainey-Smith, S.R., Masters, C.L., Ames, D., Rowe, C.C., Macaulay, S.L., Hill, A.F., Leifert, W.R., Appannah, A., Barnes, M., Barnham, K., Bedo, J., Bellingham, S., Bon, L., Bourgeat, P., Brown, B., Buckley, R., Burnham, S., Bush, A., Chandler, G., Chen, K., Clarnette, R., Collins, S., Cooke, I., Cowie, T., Cox, K., Cuningham, E., Cyarto, E., Dang, P.A.V., Darby, D., Desmond, P., Doecke, J., Dore, V., Downing, H., Dridan, B., Duesing, K., Fahey, M., Farrow, M., Faux, N., Fernandez, S., Fernando, B., Fowler, C., Fripp, J., Frost, S., Gardener, S., Gibson, S., Graham, P., Gupta, V., Hansen, D., Harrington, K., Hone, E., Horne, M., Huckstepp, B., Jones, A., Jones, G., Kamer, A., Kanagasingam, Y., Keam, L., Kowalczyk, A., Krivdic, B., Lam, C.P., Lamb, F., Lautenschlager, N., Laws, S., Lenzo, N., Leroux, H., Lftikhar, F., Li, Q-X, Lim, F., Lim, L., Lockett, L., Lucas, K., Mano, M., Marczak, C., Martins, G., Matsumoto, Y., Bird, S., McBride, S., McKay, R., Mulligan, R., Nash, T., Nigro, J., O'Keefe, G., Ong, K., Parker, B., Pedrini, S., Peiffer, J., Pejoska, S., Penny, L., Perez, K., Pertile, K., Phal, P., Porter, T., Raniga, P., Restrepo, C., Riley, M., Roberts, B., Robertson, J., Rodrigues, M., Rooney, A., Rumble, R., Ryan, T., Salvado, O., Samuel, M., Saunders, I., Savage, G., Silbert, B., Sohrabi, H.R., Syrette, J., Szoeke, C., Taddei, K., Taddei, T., Tan, S., Tegg, M., Trivedi, D., Trounson, B., Veljanovski, R., Verdile, G., Villemagne, V., Volitakis, I., Vockler, C., Vovos, M., Vrantsidis, F., Walker, S., Watt, A., Weinborn, M., Wilson, B., Woodward, M., Yastrubetskaya, O., Yates, P., Zhang, P., Chatterjee, P., Creegan, R., De Ruyck, K., Ding, H., Groth, D., Head, R., Krause, D., Lachovitzki, R., Lim, Y.Y., Lintern, T., Mondal, A., Nuttall, S., O'Callaghan, N., Osborne, L., Pang, C., Patten, G., Tuckfield, A., Varghese, J., Wilson, A., and Zhang, Q.

Abstract

Alzheimer’s disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.

Published
2016

11. The choice of psychiatry as a specialty: why do we need to pay attention?

Author

Henrique Taddei T. Barros, Ricardo Costa, and Marcos Hortes Nisihara Chagas

Subjects
medicine.medical_specialty, 020205 medical informatics, lcsh:RC435-571, media_common.quotation_subject, Population, Specialty, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Informed consent, lcsh:Psychiatry, 0202 electrical engineering, electronic engineering, information engineering, medicine, Personality, 030212 general & internal medicine, Psychiatry, education, media_common, education.field_of_study, Research ethics, Psychiatry and Mental health, Anxiety, Marital status, medicine.symptom, Psychology
Abstract

Several studies were conducted in an attempt to determine the factors that guide medical students’ specialty choice. The main factors studied include style and quality of life, financial rewards, social prestige, as well as personality characteristics and psychological profiles1. Besides these factors, the choice of psychiatry as a specialty is motivated by aspects that include: quality of education in the area during medical graduation, interest even before entering graduation, intellectual challenge, importance of doctor-patient relationship, integration opportunity with other areas, and experience from personal or family experiences of psychological and/or psychiatric problems2-4. Regarding the presence of psychiatric disorders among physicians, it is know that the suicide rate in these professionals is higher than in the general population5. Nevertheless, there are few studies that have tried to explore the associated risk factors. Considering the medical specialties, psychiatrists have high rates of suicide when compared with doctors in other specialties6, which points to the need for a careful look at this population. The purpose of this letter is to present secondary data from a study that aimed to evaluate the relationship between anxiety, social cognition and academic performance among medical students. The study design was cross-sectional and data collection was carried out among medical students from the Barretos School of Health Sciences (FACISB). This degree course was created four years ago with an annual inflow of 60 students. In the socio-demographic and academic questionnaire, besides data such as age, sex, marital status, race, and first medical specialty option, the following questions have been answered, (i) “Do you have or had any psychiatric symptoms or disorder?” and (ii) “Do you do or have done some psychiatric treatment?”. This study was approved by the Research Ethics Committee (identification: 959.395) and all participants signed an informed consent form. From 240 students, 80.3% (n = 194) completed the questionnaire. Regarding the socio-demographic data, the average age was 21.1 years (SD = ±2.33), 67.0% were female, 97.4% were single and 91.8% reported being white. Considering the questions related to symptom/disorder and psychiatric treatment, 21.1% (n = 41) of students reported having or having had some symptom or psychiatric disorder, and 19.1% (n = 37) reported that are currently doing or have already done some psychiatric treatment. Table 1 shows the odds ratio between these questions and the choice of psychiatry as their first specialization option. Table 1 shows that there is a greater chance of choosing Psychiatry among students who have or had psychiatric symptoms/ disorder and/or are doing or have done psychiatric treatment. Specific studies to evaluate the medical specialty choice had already shown the association between the choice of psychiatry and the experience of personal, familiar or close people psychological/ psychiatric problems2,3. Our study pointed to the same direction. Medical students generally have high rates of anxiety, depression and even suicidal ideation7,8, and, as mentioned earlier, psychiatry is among the medical specialties with higher suicide rates6, so it seems imperative a special attention to this group. It seems necessary a reflection by the medical schools as well as a monitoring of students through mentoring programs, to discuss the doubts and motivations of the specialty choice. It should also be emphasizing the need for more research to explore factors associated with students’ motivations in choosing the specialty, as different aspects permeate this important decision. Furthermore, others possible confounding factors should be evaluated in future studies to confirm these findings in Brazilian medical students.

Published
2016

12. Precipitating factors and decision-making processes of short-term worsening heart failure despite 'optimal' treatment (from the IN-CHF Registry)

Author

Opasich, C., Rapezzi, C., Lucci, D., Gorini, M., Pozzar, F., Zanelli, E., Tavazzi, L., Mezzani, Maggioni A. P. AND THE IN CHF Investigators: A., Bielli, M., Milanese, U., Ugliengo, G., Pozzi, R., Rabajoli, F., Bosimini, E., Valsecchi, M. G., Dadda, F., Faggiano, P., Castiglioni, G., Gibelli, G., Turelli, A. L., Belluschi, R., Bianchi, C., Emanuelli, C., Gramenzi, S., Foti, G., Agnelli, D., Volterrani, M., Moroni, E., Gara, E., Turiel, A., Recalcati, F., Valenti, D., Rusconi, F., Palvarini, M., Giusti, A., Inserra, C., Nassiacos, D., Meloni, S., Nicoli, T., Bandini, P., Moizi, M., Pedretti, R., Paolucci, M., Amati, L., Ravetta, M., Morandi, F., Provasoli, S., Planca, E., Quorso, P., Ferro, A., Pedrolli, C., Riggi, L., Tarantini, L., Candelpergher, G., Berton, G., Stefanini, M. G., Cacciavillani, L., Boffa, G. M., Mario, L., Renosto, G., Stritoni, P., Perini, G., Bonadiman, C., Varotto, L., Penzo, M., Giuliano, G., Marini, R., Barducci), E., Humar, F., Albanese, M. C., Fresco, C., Camerini, A., Griffo, R., Derchi, G., Vengo, P., Fazzini, L., Pizzorno, L., Bertoli, D., Morgagni, G., Bruno, G., Iori, E., Melandri, F., Cionini, F., Reggianini, L., Passerini, F., Del Corso, P., Rusconi, L., Marzaloni, M., Mezzetti, M., Gambarati, G. P., Mariani, P. R., Volterrani, C., Venturi, F., Zambaldi, G., Geri Brandinelli, A., Taddei, T., Dalle Luche, A., Arcuri, G., Giannini, R., Gasperini, U., Alunni, G., Bosi, E., Cocchieri, M., Severini, D., Maragoni, G., C. Ferroni, G. Saccomanno, Pasetti, L., Budini, A., Manfrin, M., Coderoni, B., Mori, A., Midi, P., D. Del Sindaco, F. Leggio, Terranova, A., Pulignano, G., Cacciatore, G., Menichelli, M., Ansalone, G., Magris, B., Scaffidi, G., Valtorta, C., Salustri, A., Amaddeo, F., Barbato, G., Aspromonte, N., Renzi, M., Mantini, L., Frattaroli, C., Mariani, A., Di Marco, G., Levantesi, G., Colonna, N., Montano, A., Di Maggio, O., Toscano, G., Capuano, V., Scherillo, M., Sensale, P., Rullo, V., Maurea, N., Miceli, D., Somelli, A., Napolitano, F., Provvisiero, P., Di Muro, M. R., Bottiglieri, P., Rufolo, F., Ciriello, N., Angelini, E., Andriulo, C., De Santis, F., Cocco, F., Zecca, A., Pennetta, A., Mariello, F., Magliari, F., De Giorgi, A., Santoro, V., Pede, S., Renna, A., De Donno, O., De Lorenzi, E., Polimeni, G., Russo, V. A., Mangia, R., Cariello, F. P., Affinita, M., Perticone, F., Cloro, C., Misuraca, G., Caporale, R., Chiappetta, P., Tripodi, E., Tassone, F., Salituri, S., Errigo, C., Meringolo, G., Donnangelo, L., Canonico, G., Coco, R., Franco, M., Coglitore, A., Donato, A., Di Tano, G., Cento, D., DE GREGORIO, Cesare, Mongiovì, M., Schillaci, A. M., Mirto, U., Clemenza, F., Ingrillì, F., Aloisi, B., Porcu, M., Pili, G., and Piras, S.

Subjects
Male, medicine.medical_specialty, Heart disease, Decision Making, Risk Factors, Internal medicine, Heart rate, Humans, Medicine, Decompensation, Prospective Studies, Registries, Practice Patterns, Physicians', Intensive care medicine, Prospective cohort study, Aged, Heart Failure, business.industry, Atrial fibrillation, Middle Aged, Prognosis, medicine.disease, Blood pressure, Heart failure, Multivariate Analysis, Emergency medicine, Ambulatory, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

This study sought to prospectively assess which factors were related to short-term worsening heart failure (HF) leading to or not to hospital admission, in long-term outpatients followed by cardiologists. The subsequent decision-making process was also analyzed. The study population consisted of 2,701 outpatients enrolled in the registry of the Italian Network on Congestive Heart Failure (IN-CHF) and followed by 133 cardiology centers (19% of all existing Italian cardiology centers). Clinical and follow-up data were collected by local trained clinicians; 215 patients (8%) had short-term decompensation (on average 2 months after the index outpatient visit). Multivariate analysis showed that previous hospitalization, long duration of symptoms, ischemic etiology, atrial fibrillation, higher functional class (New York Heart Association classification III to IV), higher heart rate, and low systolic blood pressure were independently associated with HF destabilization. Poor compliance (21%) and infection (12%) were the most frequent precipitating factors, but a precipitating factor was not identified in 40% of the patients. Poor compliance was more common in women, but no other clinical characteristics emerged as being related with a specific precipitating factor. Fifty-seven percent of the patients with a short-term recurrence of worsening HF required hospital admission; infusion treatment with inotropes and/or vasodilators was necessary in 19% of them. Long-term therapy was changed in 48% of the patients. Thus, in ambulatory HF patients, short-term worsening HF can be predicted according to the clinical characteristics on an outpatient basis. Nearly 1/3 of precipitating factors can be prevented. Patient education and avoidance of inappropriate treatment may reduce the number of relapses.

Published
2001

14. Simulation-Based Classification; a Model-Order-Reduction Approach for Structural Health Monitoring.

Author

Taddei, T., Penn, J. D., Yano, M., and Patera, A. T.

Abstract

We present a model-order-reduction approach to simulation-based classification, with particular application to structural health monitoring. The approach exploits (1) synthetic results obtained by repeated solution of a parametrized mathematical model for different values of the parameters, (2) machine-learning algorithms to generate a classifier that monitors the damage state of the system, and (3) a reduced basis method to reduce the computational burden associated with the model evaluations. Furthermore, we propose a mathematical formulation which integrates the partial differential equation model within the classification framework and clarifies the influence of model error on classification performance. We illustrate our approach and we demonstrate its effectiveness through the vehicle of a particular physical companion experiment, a harmonically excited microtruss. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
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16. Age-dependent prognostic significance of atrial fibrillation in outpatients with chronic heart failure: data from the Italian Network on Congestive Heart Failure Registry

Author

Baldasseroni, S, Orso, F, Fabbri, G, De Bernardi, A, Cirrincione, V, Gonzini, L, Fumagalli, S, Marchionni, N, Midi, P, Maggioni, Ap, Mezzani, A, Bielli, M, Milanese, U, Ugliengo, G, Pozzi, R, Rabajoli, F, Bosimini, E, Begliuomini, G, Ferrari, A, Barzizza, F, Valsecchi, Mg, Dadda, F, Faggiano, P, Castiglioni, G, Gibelli, G, Turelli, Al, Belluschi, R, Bianchi, C, Emanuelli, C, Gramenzi, S, Foti, G, Agnelli, D, Mascioli, G, Cazzani, E, Zanelli, E, Domenighini, D, Castelli, C, Moroni, E, Gara, E, Guzzetti, S, Muzzupappa, S, Turiel, M, Cappiello, E, Sandrone, G, Recalcati, F, Valenti, D, Achilli, F, Vincenzi, A, Rusconi, F, Palvarini, M, Ghio, S, Fontana, A, Giusti, A, Scelsi, L, Sebastiani, R, Ceresa, M, Nassiacos, D, Meloni, S, Nicoli, T, Bandini, P, Pedretti, R, Paolucci, M, Amati, L, Ravetta, M, Morandi, F, Provasoli, S, Bertolini, A, Imperiale, D, Agen, W, Planca, E, Quorso, P, Ferro, A, Pedrolli, C, Russo, P, Tarantini, L, Candelpergher, G, Cannarozzo, Pp, De Cian, F, Agnoli, A, Stefanini, Mg, Cacciavillani, L, Boffa, Gm, Mario, L, Renosto, G, Stritoni, P, Varotto, L, Penzo, M, Perini, G, Giuliano, G, Barducci, E, Piazza, R, Albanese, Mc, Fresco, C, Picco, F, Venturini, P, Camerini, A, Griffo, R, Derchi, G, Delfino, L, Pizzorno, L, Mazzantini, S, Torre, F, Orlandi, S, Bertoli, D, Gentile, A, Naccarella, F, Gatti, M, Coluccini, M, Morgagni, G, Alfano, G, Reggianini, L, Sansoni, S, Serra, W, Passerini, F, Del Corso, P, Rusconi, L, Marzaloni, M, Mezzetti, M, Gambarati, Gp, Mariani, Pr, Volterrani, C, Venturi, F, Zambaldi, G, Casolo, G, Moschi, G, Geri Brandinelli, A, Miracapillo, G, Boni, A, Italiani, G, Vergoni, W, Paci, Am, Lattanzi, F, Reisenhofer, B, Severini, D, Taddei, T, Dalle Luche, A, Comella, A, Gasperini, U, Cocchieri, M, Alunni, G, Bosi, E, Panciarola, R, Maragoni, G, Bardelli, G, Testarmata, P, Pasetti, L, Budini, A, Gabrilelli, D, Coderoni, B, Romaniello, C, Del Sindaco, D, Leggio, F, Terranova, A, Pulignano, G, Pozzar, F, Ansalone, G, Magris, B, Giannantoni, P, Cacciatore, G, Bottero, G, Scaffidi, G, Valtorta, C, Salustri, A, Amaddeo, F, Barbato, G, Aspromonte, N, Baldo, V, Baldo, E, Frattaroli, C, Mariani, A, Di Marco, G, Levantesi, G, Potena, Ap, Colonna, N, Montano, A, Sensale, P, Maiolica, P, Somelli, A, Napolitano, F, Provvisiero, P, Bottiglieri, P, Ciriello, N, Angelini, E, Andriulo, C, De Santis, F, Cocco, F, Zecca, A, Pennetta, A, Mariello, F, Magliari, F, De Giorgi, A, Callerame, M, Santoro, V, Pede, S, Renna, A, De Donno, O, De Lorenzi, E, Polimeni, G, Russo, Va, Mangia, R, Truncellito, L, Cariello, Fp, Affinita, M, Perticone, F, Cloro, C, Borelli, D, Matta, M, Lopresti, D, Misuraca, G, Caporale, R, Chiappetta, P, Tripodi, E, Tassone, F, Salituri, S, Errigo, C, Meringolo, G, Donnangelo, L, Canonico, G, Coco, R, Franco, M, Coglitore, A, Donato, A, Di Tano, G, Cento, D, DE GREGORIO, Cesare, Mongiovì, M, Schillaci, Am, Mirto, U, Clemenza, F, Ingrillì, F, Cavallaro, A, Aloisi, B, Ledda, G, Rizzo, C, Porcu, M, Salis, S, Pistis, L, Pili, G, Piras, S, Maoddi, I, and Uras, F.

Subjects
Male, medicine.medical_specialty, Adrenergic beta-Antagonists, Age dependent, Angiotensin-Converting Enzyme Inhibitors, VENTRICULAR SYSTOLIC DYSFUNCTION, POPULATION-BASED COHORT, Age Distribution, Older patients, Internal medicine, Atrial Fibrillation, Outpatients, medicine, Humans, Pharmacology (medical), Registries, Aged, Heart Failure, business.industry, Network on, Anticoagulants, Atrial fibrillation, Middle Aged, medicine.disease, Prognosis, Death, Sudden, Cardiac, Italy, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Anti-Arrhythmia Agents
Abstract

Objectives: The role of atrial fibrillation (AF) in older patients with heart failure (HF) is controversial because many variables seem to influence their outcome. We investigated the predictivity of AF in 3 age groups of outpatients with HF. Methods: We analyzed 8,178 outpatients enrolled in the Italian Network on Congestive Heart Failure Registry with HF diagnosed according to the European Society of Cardiology criteria. A trained cardiologist established the diagnosis of AF and HF at the entry visit at each center. We stratified the population into 3 age groups, as follows: group A, ≤65 years; group B, 66–75 years, and group C, >75 years. Results: Group A was composed of 4,261 patients, 683 with AF (16.0%); in group B there were 2,651 patients, 638 with AF (24.1%), and group C was composed of 1,266 patients, 412 with AF (32.5%). The 1-year mortality rate was higher in AF patients in all groups. In a multivariate model, AF remained an independent risk factor for death in groups A and B, but not in group C [group A: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.10–1.81; group B: HR 1.29, 95% CI 1.00–1.67; group C: HR 1.05, 95% CI 0.78–1.43]. Conclusion: The prevalence of AF increased with age and was associated with a higher mortality rate. However, AF independently predicted all-cause mortality only in patients aged ≤75 years.

Published
2010

17. Physical activity and amyloid-β plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing

Author

Brown, B.M., Peiffer, J.J., Taddei, K., Lui, J.K., Laws, S.M., Gupta, V.B., Taddei, T., Ward, V.K., Rodrigues, M.A., Burnham, S., Rainey-Smith, S.R., Villemagne, V.L., Bush, A., Ellis, K.A., Masters, C.L., Ames, D., Macaulay, S.L., Szoeke, C., Rowe, C.C., Martins, R.N., Brown, B.M., Peiffer, J.J., Taddei, K., Lui, J.K., Laws, S.M., Gupta, V.B., Taddei, T., Ward, V.K., Rodrigues, M.A., Burnham, S., Rainey-Smith, S.R., Villemagne, V.L., Bush, A., Ellis, K.A., Masters, C.L., Ames, D., Macaulay, S.L., Szoeke, C., Rowe, C.C., and Martins, R.N.

Abstract

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-β (Aβ) and Aβ brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aβ and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ɛ4 allele. Five-hundred and forty six cognitively intact participants (aged 60–95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aβ levels were measured in fasting blood samples. A subgroup (n=116) underwent 11C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aβ1−42/1−40 ratio (P=0.001). After stratification of the cohort based on APOE ɛ4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aβ from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ɛ4 carriers. Lower plasma Aβ1−42/1−40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.

Published
2013

18. Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease

Author

Doecke, J.D., Laws, S.M., Faux, N.G., Wilson, W., Burnham, S.C., Lam, C.P., Mondal, A., Bedo, J., Bush, A.I., Brown, B., De Ruyck, K., Ellis, K.A., Fowler, C., Gupta, V.B., Head, R., Macaulay, S.L., Pertile, K., Rowe, C.C., Rembach, A., Rodrigues, M., Rumble, R., Szoeke, C., Taddei, K., Taddei, T., Trounson, B., Ames, D., Masters, C.L., Martins, R.N., Doecke, J.D., Laws, S.M., Faux, N.G., Wilson, W., Burnham, S.C., Lam, C.P., Mondal, A., Bedo, J., Bush, A.I., Brown, B., De Ruyck, K., Ellis, K.A., Fowler, C., Gupta, V.B., Head, R., Macaulay, S.L., Pertile, K., Rowe, C.C., Rembach, A., Rodrigues, M., Rumble, R., Szoeke, C., Taddei, K., Taddei, T., Trounson, B., Ames, D., Masters, C.L., and Martins, R.N.

Abstract

Objective To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). Design Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. Setting General community-based, prospective, longitudinal study of aging. Participants A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. Results A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β2 microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. Conclusions This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis. Alzheimer disease (AD) is the most common form of dementia, affecting more than 27 million persons worldwide and predicted to affect 86 million people by the

Published
2012

19. Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: Baseline characteristics in subjects of the australian imaging biomarker lifestyle study.

Author

Faux N.G., Rembach A., Rowe C.C., Rumble R.L., Szoeke C., Taddei K., Taddei T., Trounson B.O., Villemagne V.L., Ward V., Ames D., Masters C.L., Bush A.I., Ellis K.A., Porter L., Fowler C.J., Laws S.M., Martins R.N., Pertile K.K., Faux N.G., Rembach A., Rowe C.C., Rumble R.L., Szoeke C., Taddei K., Taddei T., Trounson B.O., Villemagne V.L., Ward V., Ames D., Masters C.L., Bush A.I., Ellis K.A., Porter L., Fowler C.J., Laws S.M., Martins R.N., and Pertile K.K.

Abstract

There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (-10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate. © 2011-IOS Press and the authors. All rights reserved.

Published
2012

20. Blood-based protein biomarkers for diagnosis of Alzheimer disease

Author

Doecke, JD, Laws, SM, Faux, NG, Wilson, W, Burnham, SC, Lam, CP, Mondal, A, Bedo, J, Bush, AI, Brown, B, De Ruyck, K, Ellis, KA, Fowler, C, Gupta, Veer, Head, R, Macaulay, SL, Pertile, K, Rowe, CC, Rembach, A, Rodrigues, M, Rumble, R, Szoeke, C, Taddei, K, Taddei, T, Trounson, B, Ames, D, Masters, CL, Martins, RN, Doecke, JD, Laws, SM, Faux, NG, Wilson, W, Burnham, SC, Lam, CP, Mondal, A, Bedo, J, Bush, AI, Brown, B, De Ruyck, K, Ellis, KA, Fowler, C, Gupta, Veer, Head, R, Macaulay, SL, Pertile, K, Rowe, CC, Rembach, A, Rodrigues, M, Rumble, R, Szoeke, C, Taddei, K, Taddei, T, Trounson, B, Ames, D, Masters, CL, and Martins, RN

Published
2012

21. Systemic therapy in hepatocellular carcinoma

Author

Wrzesinski, S, Taddei, T, Strazzabosco, M, Wrzesinski, SH, Taddei, TH, STRAZZABOSCO, MARIO, Wrzesinski, S, Taddei, T, Strazzabosco, M, Wrzesinski, SH, Taddei, TH, and STRAZZABOSCO, MARIO

Abstract

Many potential systemic therapies are being investigated for the treatment of hepatocellular carcinoma (HCC). The incidence of this malignancy is rising sharply and the vast majority of patients present at advanced stages. Although the earlier dismal results with cytotoxic chemotherapies made way for the development of locoregional therapies that provided improved overall survival, truly personalized therapy will require the selection of phenotypically similar stages of disease and populations, an understanding of the complex molecular and genetic pathways leading to HCC, and a keen understanding of the pathobiology of cirrhosis. Only then will we understand how to offer a particular patient at a specific stage of disease the appropriate therapy to truly prolong survival.

Published
2011

22. Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Author

Lui, J.K., Laws, S.M., Li, Q-X, Villemagne, V.L., Ames, D., Brown, B., Bush, A.I., De Ruyck, K., Dromey, J., Ellis, K.A., Faux, N.G., Foster, J., Fowler, C., Gupta, V., Hudson, P., Laughton, K., Masters, C.L., Pertile, K., Rembach, A., Rimajova, M., Rodrigues, M., Rowe, C.C., Rumble, R., Szoeke, C., Taddei, K., Taddei, T., Trounson, B., Ward, V., Martins, R.N., Lui, J.K., Laws, S.M., Li, Q-X, Villemagne, V.L., Ames, D., Brown, B., Bush, A.I., De Ruyck, K., Dromey, J., Ellis, K.A., Faux, N.G., Foster, J., Fowler, C., Gupta, V., Hudson, P., Laughton, K., Masters, C.L., Pertile, K., Rembach, A., Rimajova, M., Rodrigues, M., Rowe, C.C., Rumble, R., Szoeke, C., Taddei, K., Taddei, T., Trounson, B., Ward, V., and Martins, R.N.

Abstract

Amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Aβ as an AD biomarker and its relationship with Aβ load and to determine the effect of different assay methods on the interpretation of Aβ levels. Plasma Aβ1-40, Aβ1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Aβ levels were compared to Aβ load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Aβ1-42 and Aβ1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Aβ load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Aβ isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Aβ has diagnostic value in a panel of biomarkers.

Published
2010

23. Plasma Amyloid-beta as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Author

Lui, J., Laws, S., Li, Q., Villemagne, V., Ames, D., Brown, B., Bush, A., De Ruyck, K., Dromey, J., Ellis, K., Faux, N., Foster, Jonathan, Fowlor, C., Gupta, V., Hudson, P., Laughton, K., Masters, C., Pertile, K., Rembach, A., Rimajova, M., Rodrigues, M., Rowe, C., Rumble, R., Szoeke, C., Taddei, K., Taddei, T., Trounson, B., Ward, V., Martins, R., Lui, J., Laws, S., Li, Q., Villemagne, V., Ames, D., Brown, B., Bush, A., De Ruyck, K., Dromey, J., Ellis, K., Faux, N., Foster, Jonathan, Fowlor, C., Gupta, V., Hudson, P., Laughton, K., Masters, C., Pertile, K., Rembach, A., Rimajova, M., Rodrigues, M., Rowe, C., Rumble, R., Szoeke, C., Taddei, K., Taddei, T., Trounson, B., Ward, V., and Martins, R.

Abstract

Amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Aβ as an AD biomarker and its relationship with Aβ load and to determine the effect of different assay methods on the interpretation of Aβ levels. Plasma Aβ1-40, Aβ1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Aβ levels were compared to Aβ load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Aβ1-42 and Aβ1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Aβ load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Aβ isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Aβ has diagnostic value in a panel of biomarkers.

Published
2010

24. The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer’s disease

Author

Ellis, K., Bush, A., Darby, D., de Fazio, D., Foster, Jonathan, Hudson, P., Lautenschlager, N., Lenzo, N., Martins, R., Maruff, P., Masters, C., Milner, A., Pike, K., Rowe, C., Savage, G., Szoeke, C., Taddei, K., Villemagne, V., Woodward, M., Ames, D., Acosta, O., Ames, J., Agarwal, M., Bahar-Fuchs, A., Baxendale, D., Bechta-Metti, K., Bevage, C., Bevege, L., Bourgeat, P., Brown, B., Clarnette, R., Cowie, T., Crowley, K., Currie, A., El- Sheikh, D., Dickinson, K., Farrow, M., Faux, N., Fripp, J., Fowler, C., Gupta, V., Jones, G., Khoo, J., Killedar, A., Killeen, N., Kim, T.W., Kotsopoulos, E., Lachovitzki, R., Li, Q., Liang, X., Lucas, K., Lui, J., Martins, G., Montague, C., Moore, L., Muir, A., O’Halloran, C., O’Keefe, G., Panayiotou, A., Paton, A., Paton, J., Peiffer, J., Pejoska, S., Pertile, K., Porter, L., Price, R., Raniga, P., Rees, G., Rembach, A., Rimajova, M., Robins, P., Ronsisvalle, E., Rumble, R., Rodrigues, M., Salvado, O., Sach, J., Samuel, M., Sittironnarit, G., Taddei, T., Trivedi, D., Trounson, B., Tsikkos, M., Walker, S., Ward, V., Yastrubetskaya, O., Ellis, K., Bush, A., Darby, D., de Fazio, D., Foster, Jonathan, Hudson, P., Lautenschlager, N., Lenzo, N., Martins, R., Maruff, P., Masters, C., Milner, A., Pike, K., Rowe, C., Savage, G., Szoeke, C., Taddei, K., Villemagne, V., Woodward, M., Ames, D., Acosta, O., Ames, J., Agarwal, M., Bahar-Fuchs, A., Baxendale, D., Bechta-Metti, K., Bevage, C., Bevege, L., Bourgeat, P., Brown, B., Clarnette, R., Cowie, T., Crowley, K., Currie, A., El- Sheikh, D., Dickinson, K., Farrow, M., Faux, N., Fripp, J., Fowler, C., Gupta, V., Jones, G., Khoo, J., Killedar, A., Killeen, N., Kim, T.W., Kotsopoulos, E., Lachovitzki, R., Li, Q., Liang, X., Lucas, K., Lui, J., Martins, G., Montague, C., Moore, L., Muir, A., O’Halloran, C., O’Keefe, G., Panayiotou, A., Paton, A., Paton, J., Peiffer, J., Pejoska, S., Pertile, K., Porter, L., Price, R., Raniga, P., Rees, G., Rembach, A., Rimajova, M., Robins, P., Ronsisvalle, E., Rumble, R., Rodrigues, M., Salvado, O., Sach, J., Samuel, M., Sittironnarit, G., Taddei, T., Trivedi, D., Trounson, B., Tsikkos, M., Walker, S., Ward, V., and Yastrubetskaya, O.

Abstract

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants. Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning. Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring. Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.

Published
2009

28. Amyloid-β and its relevance to the detection of Alzheimer's disease in blood plasma: Findings from the first phase of the Australian Imaging, Biomarker and Lifestyle (AIBL) Flagship Study of Aging

Author

Lui, J., primary, Li, Q., additional, De Ruyck, K., additional, Gupta, V., additional, Taddei, K., additional, Foster, J., additional, Taddei, T., additional, Brown, B., additional, Ward, V., additional, Rodrigues, M., additional, Rimajova, M., additional, Ellis, K., additional, Rowe, C., additional, Villemagne, V., additional, Hudson, P., additional, Masters, C., additional, Ames, D., additional, and Martins, R., additional

Published
2009
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29. [Changes in the wall motion of left ventricle in dipyridamole-induced ischemic cardiopathy studied by nuclear magnetic resonance. A comparison with myocardial scintigraphy with 99mTc MIBI]

Author

Casolo, Gc, Bonechi, F., Taddei, T., Fortini, A., Dabizzi, Rp, Bisi, Gianni, Gensini, Gf, and Malfanti, Pl

Subjects
Technetium Tc 99m Sestamibi, Tomography, Emission-Computed, Single-Photon, Heart Ventricles, Myocardium, Motion Pictures, Contrast Media, Coronary Disease, Heart, Dipyridamole, Organotechnetium Compounds, Magnetic Resonance Imaging, Electrocardiography, Evaluation Studies as Topic, Nitriles, Humans
Abstract

To investigate whether magnetic resonance imaging (NMR) can detect alterations in LV contractility during myocardial ischemia, ten patients aged 32-72 with coronary artery disease underwent ECG gated NMR performed at 0.5 Tesla after intravenous infusion of high dose dipyridamole (DP) (0.7 mg/Kg) over 5 minutes. LV contraction in planes similar to echo short axis projection was imaged under condition, 3' and 15-20' after infusion of DP by fast multiphasic imaging (FMI), multiple angulated cine-NMR sequence with a temporal resolution of 50 m/sec. Entity and size of perfusion defects after DP were determined by Tc 99m MIBI myocardial scintigraphy. In all patients changes in LV contractility appeared at NMR in the same site of perfusion impairments revealed with MIBI. In 8 patients the alterations lasted even more than 20' after the first NMR scan. NMR provides the opportunity of performing long-lasting assessment of ventricular wall contractility and enables to exactly localize the site and extension of kinetic changes as well as their time of onset and time duration.

Published
1991

30. Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study.

Author

Faux NG, Ellis KA, Porter L, Fowler CJ, Laws SM, Martins RN, Pertile KK, Rembach A, Rowe CC, Rumble RL, Szoeke C, Taddei K, Taddei T, Trounson BO, Villemagne VL, Ward V, Ames D, Masters CL, Bush AI, and Faux, Noel G

Abstract

There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (-10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate. [ABSTRACT FROM AUTHOR]

Published
2011
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32. High content, multi-parameter analyses in buccal cells to identify alzheimer’s disease

Author

François, M., Fenech, M. F., Thomas, P., Hor, M., Rembach, A., Martins, R. N., Rainey-Smith, S. R., Masters, C. L., Ames, D., Rowe, C. C., Lance Macaulay, S., Hill, A. F., Leifert, W. R., Appannah, A., Barnes, M., Barnham, K., Bedo, J., Bellingham, S., Bon, L., Bourgeat, P., Brown, B., Buckley, R., Burnham, S., Bush, A., Chandler, G., Chen, K., Clarnette, R., Collins, S., Cooke, I., Cowie, T., Cox, K., Cuningham, E., Cyarto, E., Dang, P. A. V., Darby, D., Desmond, P., Doecke, J., Dore, V., Downing, H., Dridan, B., Duesing, K., Fahey, M., Farrow, M., Faux, N., Fenech, M., Fernandez, S., Fernando, B., Fowler, C., Francois, M., Fripp, J., Frost, S., Gardener, S., Gibson, S., Graham, P., Gupta, V., Hansen, D., Harrington, K., Hill, A., Hone, E., Horne, M., Huckstepp, B., Jones, A., Jones, G., Kamer, A., Kanagasingam, Y., Keam, L., Kowalczyk, A., Krivdic, B., Lam, C. P., Lamb, F., Lautenschlager, N., Laws, S., Leifert, W., Lenzo, N., Leroux, H., Lftikhar, F., Li, Q. -X, Lim, F., Lim, L., Lockett, L., Lucas, K., Mano, M., Marczak, C., Martins, G., Maruff, P., Matsumoto, Y., Bird, S., Mcbride, S., Mckay, R., Mulligan, R., Nash, T., Nigro, J., O Keefe, G., Ong, K., Parker, B., Pedrini, S., Peiffer, J., Pejoska, S., Penny, L., Perez, K., Pertile, K., Phal, P., Porter, T., Rainey-Smith, S., Raniga, P., Restrepo, C., Riley, M., Roberts, B., Robertson, J., Rodrigues, M., Rooney, A., Rumble, R., Ryan, T., Salvado, O., Samuel, M., Saunders, I., Savage, G., Silbert, B., Sohrabi, H., Syrette, J., Cassandra Szoeke, Taddei, K., Taddei, T., Tan, S., Tegg, M., Trivedi, D., Trounson, B., Veljanovski, R., Verdile, G., Villemagne, V., Volitakis, I., Vockler, C., Vovos, M., Vrantsidis, F., Walker, S., Watt, A., Weinborn, M., Wilson, B., Woodward, M., Yastrubetskaya, O., Yates, P., Zhang, P., Chatterjee, P., Creegan, R., Ruyck, K., Ding, H., Groth, D., Head, R., Krause, D., Lachovitzki, R., Lim, Y. Y., Lintern, T., Mondal, A., Nuttall, S., O Callaghan, N., Osborne, L., Pang, C., Patten, G., Tuckfield, A., Varghese, J., Wilson, A., and Zhang, Q.

33. Reduced Basis Techniques For Nonlinear Conservation Laws

Author

Taddei, T., Perotto, Simona, and Quarteroni, ALFIO MARIA

Subjects
Nonlinear conservation laws, reduced basis method, model reduction, ComputingMethodologies_COMPUTERGRAPHICS
Abstract

In this paper we present a new reduced basis technique for parametrized nonlinear scalar conservation laws in presence of shocks. The essential ingredients are an efficient algorithm to approximate the shock curve, a procedure to detect the smooth components of the solution at the two sides of the shock, and a suitable interpolation strategy to reconstruct such smooth components during the online stage. The approach we propose is based on some theoretical properties of the solution to the problem. Some numerical examples prove the effectiveness of the proposed strategy.

34. A low pulse pressure is an independent predictor of mortality in heart failure: Data from a large nationwide cardiology database (IN-CHF registry)

Author

Schillaci, Giuseppe, Di Luzio, Silvia, Coluccini, Mario, Gonzini, Lucio, Porcu, Maurizio, Pozzar, Francesco, Maggioni, Aldo P, Investigators, Mezzani, A, Bielli, M, Milanese, U, Ugliengo, G, Pozzi, R, Rabajoli, F, Bosimini, E, Begliuomini, G, Ferrari, A, Barzizza, F, Valsecchi, Mg, Dadda, F, Faggiano, P, Castiglioni, G, Gibelli, G, Turelli, Al, Belluschi, R, Bianchi, C, Emanuelli, C, Gramenzi, S, Foti, G, Agnelli, D, Mascioli, G, Cazzani, E, Zanelli, E, Domenighini, D, Castelli, C, Moroni, E, Gara, S, Guzzetti, S, Muzzupappa, S, Turiel, M, Cappiello, E, Sandrone, G, Recalcati, F, Valenti, D, Achilli, F, Vincenzi, A, Rusconi, F, Palvarini, M, Ghio, S, Fontana, A, Giusti, A, Scelsi, L, Sebastiani, R, Ceresa, M, Nassiacos, D, Meloni, S, Nicoli, T, Bandini, P, Pedretti, R, Paolucci, M, Amati, L, Ravetta, M, Morandi, F, Provasoli, S, Bertolini, A, Imperiale, D, Agen, W, Planca, E, Quorso, P, Ferro, A, Pedrolli, C, Russo, P, Tarantini, L, Candelpergher, G, Cannarozzo, Pp, De Cian, F, Agnoli, A, Stefanini, Mg, Cacciavillani, L, Boffa, Gm, Mario, L, Renosto, G, Stritoni, P, Varotto, L, Penzo, M, Perini, G, Giuliano, G, Barducci, E, Piazza, R, Albanese, Mc, Fresco, C, Picco, F, Venturini, P, Camerini, A, Griffo, R, Derchi, G, Delfino, L, Pizzorno, L, Mazzantini, S, Torre, F, Orlandi, S, Bertoli, D, Gentile, A, Naccarella, F, Gatti, M, Coluccini, M, Morgagni, G, Alfano, G, Reggianini, L, Sansoni, S, Serra, W, Passerini, F, Del Corso, P, Rusconi, L, Marzaloni, M, Mezzetti, M, Gambarati, Gp, Mariani, Pr, Volterrani, C, Venturi, F, Zambaldi, G, Casolo, G, Moschi, G, Geri Brandinelli, G, Miracapillo, G, Boni, A, Italiani, G, Vergoni, W, Paci, Ap, Lattanzi, F, Reisenhofer, B, Severini, D, Taddei, T, Dalle Luche, A, Comella, A, Gasperini, U, Cocchieri, M, Alunni, G, Bosi, E, Panciarola, R, Maragoni, G, Bardelli, G, Testarmata, P, Pasetti, L, Budini, A, Gabrielli, D, Coderoni, B, Midi, P, Romaniello, C, Del Sindaco, D, Leggio, F, Terranova, A, Pulignano, G, Pozzar, P, Ansalone, G, Magris, B, Giannantoni, P, Cacciatore, G, Bottero, G, Scaffidi, G, Valtorta, C, Salustri, A, Amaddeo, F, Barbato, G, Aspromonte, N, Baldo, V, Baldo, E, Frattaroli, C, Mariani, A, Di Marco, G, Levantesi, G, Potena, Ap, Colonna, N, Montano, A, Sensale, P, Maiolica, O, Somelli, A, Napolitano, F, Provvisiero, P, Bottiglieri, P, Ciriello, N, Angelini, E, Andriulo, C, De Santis, F, Cocco, F, Pennetta, A, Mariello, F, Magliari, F, De Giorgi, A, Callerame, M, Santoro, V, Pede, S, Renna, A, De Donno, O, De Lorenzi, E, Polimeni, V, Russo, Va, Mangia, R, Truncellito, L, Cariello, Fp, Affinita, M, Perticone, F, Cloro, C, Borelli, D, Matta, M, Lopresti, D, Misuraca, A, Caporale, R, Chiappetta, P, Tripodi, E, Tassone, F, Salituri, S, Errigo, C, Meringolo, G, Donnangelo, L, Canonico, G, Coco, R, Franco, M, Coglitore, A, Donato, A, Di Tano, G, Cento, D, DE GREGORIO, Cesare, Mongiovì, M, Schillaci, Am, Mirto, U, Clemenza, F, Ingrillì, F, Cavallaro, A, Aloisi, B, Ledda, G, Rizzo, C, Porcu, M, Salis, S, Pistis, L, Pili, G, Piras, S, Maoddi, I, and Uras, F.

Subjects
Adult, Male, medicine.medical_specialty, Blood Pressure, Independent predictor, Low pulse pressure, Predictive Value of Tests, Internal medicine, Humans, Medicine, Aged, Female, Follow-Up Studies, Heart Failure, Italy, Middle Aged, Pulse, Registries, Stroke Volume, business.industry, medicine.disease, Heart failure, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract

A high pulse pressure (PP) predicts cardiovascular mortality in hypertension and in the elderly. We analyzed the data from the Italian Network of Congestive Heart Failure Registry to test the prognostic role of PP in patients with heart failure.A total of 8660 patients with heart failure (mean age 64 +/- 12 years, 73% male) were divided into four groups according to their PP (40, 40-49, 50-59, andor = 60 mmHg), and followed prospectively.After 1 year, 995 patients (11.5%) died. Both the mean arterial pressure and systolic blood pressure were found to be inversely associated with mortality at univariate and multivariate analyses. An inverse univariate relation was observed between PP and all-cause mortality. An excess mortality risk in the lowest PP group (odds ratio 1.40, 95% confidence interval 1.09-1.79 vs the highest PP group) was confirmed in a multivariate analysis which took into account the effect of several other variables, including mean arterial pressure. Similar findings were obtained for cardiovascular mortality. When we replaced systolic blood pressure with mean arterial pressure in the model, PP did not retain its independent prognostic role, possibly because of the high co-linearity between these two variables (r = 0.87).For any given level of mean arterial pressure, a low PP is an independent predictor of all-cause and cardiovascular death in patients with heart failure. The association may be partly related to the strong influence of low systolic blood pressure on mortality. Different pathophysiological mechanisms may underlie the opposite prognostic significance of PP in hypertension and heart failure.

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36. Hepatic Venous Pressure Gradient (HVPG), Serum Sodium (SNa), and Model of End-stage Liver Disease Score (MELD)

Author

Mario Strazzabosco, Tamar H. Taddei, Taddei, T, and Strazzabosco, M

Subjects
medicine.medical_specialty, Pathology, business.industry, Sodium, Portal venous pressure, Gastroenterology, MELD score, chemistry.chemical_element, Hepatic venous pressure gradient, End stage liver disease, liver, Text mining, chemistry, MED/12 - GASTROENTEROLOGIA, Internal medicine, medicine, business
Published
2007

37. Systemic therapy in hepatocellular carcinoma

Author

Mario Strazzabosco, Stephen H. Wrzesinski, Tamar H. Taddei, Wrzesinski, S, Taddei, T, and Strazzabosco, M

Subjects
Oncology, medicine.medical_specialty, Pathology, Cirrhosis, Carcinoma, Hepatocellular, medicine.medical_treatment, Antineoplastic Agents, Disease, Malignancy, Systemic therapy, Article, Liver Neoplasms, Experimental, MED/12 - GASTROENTEROLOGIA, Internal medicine, medicine, Carcinoma, Animals, Humans, Stage (cooking), Chemotherapy, Clinical Trials as Topic, Hepatology, business.industry, Liver Neoplasms, hepatocellular carcinoma, liver, medicine.disease, Hepatocellular carcinoma, business
Abstract

Many potential systemic therapies are being investigated for the treatment of hepatocellular carcinoma (HCC). The incidence of this malignancy is rising sharply and the vast majority of patients present at advanced stages. Although the earlier dismal results with cytotoxic chemotherapies made way for the development of locoregional therapies that provided improved overall survival, truly personalized therapy will require the selection of phenotypically similar stages of disease and populations, an understanding of the complex molecular and genetic pathways leading to HCC, and a keen understanding of the pathobiology of cirrhosis. Only then will we understand how to offer a particular patient at a specific stage of disease the appropriate therapy to truly prolong survival.

Published
2011

38. Clinicopathologic features and prognosis of steatohepatitic hepatocellular carcinoma based on varying cutoffs of tumoral steatohepatitic changes.

Author

Zhang T, Niu N, Taddei T, Jain D, and Zhang X

Abstract

Objectives: Steatohepatitic hepatocellular carcinoma (SH-HCC) is currently recognized as a distinct histologic subtype of HCC. The prognosis and specific criteria for determining the amount of steatohepatitis required to define SH-HCC are still unclear., Methods: After excluding all recognized HCC subtypes from 505 HCC cases (2010-2019), the remaining cases were categorized as conventional HCC (CV-HCC) (n = 223). The cases classified as SH-HCC (n = 171) were further divided into groups based on the percentage of steatohepatitis: 5% or more, 30% or more, and 50% or more., Results: Hepatitis C virus infection was the predominant underlying liver disease in both the CV-HCC and SH-HCC groups. Metabolic dysfunction-associated steatotic liver disease (formerly nonalcoholic fatty liver disease) was more prevalent in all cases of SH-HCC with different steatohepatitic cutoffs than in cases of CV-HCC. There were no differences in the stage of fibrosis of the background liver between the CV-HCC and SH-HCC groups. SH-HCC with different cutoffs exhibited a notable increase in the presence of glycogenated nuclei, Mallory-Denk bodies, and hyaline globules in tumor cells. Survival analysis did not reveal substantial differences in overall survival between the CV-HCC and SH-HCC groups and among patients with SH-HCC with different steatohepatitis cutoffs., Conclusions: The degree of intratumoral steatohepatitis in patients with SH-HCC does not appear to be a notable prognostic factor. The presence of steatohepatitis in the tumor is better recognized as 1 of the histopathologic patterns of HCC., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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39. A Crisis in Scope: Recruitment and Retention Challenges Reported by VA Gastroenterology Section Chiefs.

Author

von Rosenvinge EC, Vela SA, Paine ER, Chang MF, Hanson BJ, Taddei T, Smalley WE, Dunbar KB, Khan NH, Kahng LS, Anwar J, Zing R, Gawron A, Dominitz JA, and Baffy G

Abstract

Background: Having a sufficient number of gastroenterologists is important for protecting the digestive health of veterans. However, gastroenterology is among the most difficult medical specialties for recruitment at the US Department of Veterans Affairs (VA)., Methods: We surveyed VA gastroenterology section chiefs to learn about current barriers to recruitment and retention and to identify opportunities for improvement., Results: Of 131 VA gastroenterology section chiefs at VA medical centers who received the survey, 55 responded (42%). Thirty-six respondents (65%) reported current vacancies at their facilities (range, 1-4). Low salary and human resources challenges were the most frequently reported barriers to recruitment. Low salary and administrative burden, including lack of sufficient support staff, were the most frequently reported barriers to retention., Conclusions: While salary is the most frequently reported barrier to recruitment and retention, human resources challenges represent the second-most frequently reported barrier to recruitment. Administrative burden linked to suboptimal staffing support is the second most frequently reported barrier to retention. Efforts to raise salaries (higher than the current $400,000 ceiling), streamline human resources processes, and reduce administrative burden are needed to ensure a thriving VA gastroenterology workforce., Competing Interests: Author disclosures: Brian Hanson served as a consultant for Motus GI. The other authors have no conflicts to disclose., (Copyright © 2024 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Published
2024
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42. Safety of naltrexone in patients with cirrhosis.

Author

Thompson R, Taddei T, Kaplan D, and Rabiee A

Abstract

Background & Aims: Treatment of alcohol use disorder (AUD) improves survival in patients with alcohol-related cirrhosis. However, medications for alcohol use disorder (MAUD) are underutilized in this population, partially due to concerns regarding drug-induced liver injury (DILI). Our aim was to evaluate the safety of naltrexone in patients with cirrhosis., Methods: This was a retrospective study of patients with cirrhosis who were prescribed naltrexone using the VOCAL (Veterans Outcomes and Costs Associated with Liver Disease) database. Patients with new initiation of naltrexone after diagnosis of cirrhosis who had liver enzymes checked within a 3-month time frame were included. A chart review was performed on patients who developed alanine aminotransferase or alkaline phosphatase elevations to more than 2× or 5× the upper limit of normal, respectively. The RUCAM (Roussel Uclaf causality assessment method) was used to determine if DILI occurred., Results: A total of 3,285 patients with cirrhosis were initiated on naltrexone, of whom 2,940 had laboratory testing during the high-risk DILI period. Only 2% of patients had liver enzyme elevations, and among those, 30 (48%) were classified as "DILI excluded" and 32 (52%) were classified as "DILI unlikely". No patients were classified as possible, probable, or highly probable DILI. No deaths or new decompensations were attributed to naltrexone., Conclusions: Naltrexone in patients with cirrhosis was not associated with development of DILI using RUCAM scoring. Naltrexone appears to be safe in patients with compensated and decompensated cirrhosis., Impact and Implications: Naltrexone is an effective medication for treating alcohol use disorder but is underutilized in patients with underlying liver disease due to historical concerns regarding hepatotoxicity. This retrospective study shows no drug-induced liver injury in a large cohort of patients with cirrhosis with new initiation of naltrexone. This study may encourage providers to prescribe naltrexone to patients with existing liver disease with ongoing alcohol use disorder.

Published
2024
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43. Detection of hepatocellular carcinoma methylation markers in salivary DNA.

Author

Mezzacappa C, Wang Z, Lu L, Risch H, Taddei T, and Yu H

Subjects
Adult, Humans, DNA Methylation genetics, Cell Cycle Proteins genetics, DNA metabolism, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Liver Neoplasms diagnosis, Liver Neoplasms genetics, Liver Neoplasms metabolism
Abstract

Background: Alterations to DNA methylation have been identified in both hepatocellular carcinoma (HCC) tumor and circulating DNA from affected individuals. These markers have potential utility in HCC screening. Adherence to HCC screening is poor and acceptable HCC screening tests are needed., Methods: A feasibility study was performed on a subset of case patients and control subjects from a prior study of risk factors for HCC. Case patients (n=12) included adults aged 47-85 years with a first diagnosis of HCC between 2011 and 2016 and without viral hepatitis. Control subjects (n=12) were matched on age, sex, and state of residence. Participants provided saliva samples for DNA genotyping. Log fold change in salivary DNA methylation at 1359 CpG sites representing 25 candidate genes previously associated with HCC was compared across case patients and control subjects., Results: The quantity of DNA ranged from 9.65 to 257.79 μg. The purity of DNA isolates was good, with mean OD260/280 ratio of 1.78 (SD: 0.14). Of 25 candidate genes, 16 had at ≥1 CpG site with detectable differences in methylation across HCC case patients and control subjects. Sites differentially methylated in HCC case patients included genes encoding tumor suppressors (PRDM2, RUNX3, p15/16, and RASSF1/5), regulators of cell cycle progression (DAPK1 and TP73), and DNA repair (MGMT and GSTP1). No associations met the significance threshold 3.7 × 10-5 required for multiple comparisons., Conclusions: Salivary DNA may be a feasible alternative to blood samples in the era of novel DNA-based screening tests for HCC. The ease of saliva-based testing supports further investigation of its potential., (© 2024 The Author(s).)

Published
2024
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44. Rates, patterns, and predictors of specialty palliative care consultation among patients with acute-on-chronic liver failure.

Author

Patel A, Walling A, Kanwal F, Serper M, Hernaez R, Sundaram V, Kaplan D, Taddei T, and Mahmud N

Abstract

Background & Aims: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described., Methods: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, and facility-level variation on receipt of palliative care consultation., Results: We identified 21,987 patients hospitalized with ACLF, of whom 30.5% received specialty palliative care consultation. Higher ACLF grade (ACLF-2 [odds ratio (OR) 1.82, 95% CI 1.67-1.99], ACLF-3 [OR 3.06, 95% CI 2.76-3.40]), prior specialty palliative care consultation (OR 2.62, 95% CI 2.36-2.91), and hepatocellular carcinoma (OR 2.10, 95% CI 1.89-2.33) were associated with consultation. Consultation occurred latest and closest to the time of death for patients with ACLF-3 compared to ACLF-1 and ACLF-2. Significant facility-level variation in consultation persisted among patients with ACLF-3, despite adjusting for multiple patient and facility factors., Conclusion: In this large cohort of hospitalized patients with ACLF, specialty palliative care consultation was rare, more common in patients with higher grade ACLF, and tended to occur closer to the time of death for the sickest patients. Greater attention should be placed on earlier integration of palliative care during acute hospitalizations in patients with ACLF., Impact and Implications: Though palliative care consultation is recommended for patients with acute-on-chronic liver failure, there is no data demonstrating how often this occurs during hospitalizations, on a population level. We found that consultation occurs in only 30.5% of patients and occurs later for patients with grade 3 acute-on-chronic liver failure. Our data should provoke clinicians to urgently consider quality improvement efforts to integrate palliative care into the management of these seriously ill patients., Competing Interests: The authors of this manuscript have no conflicts of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.

Published
2023
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45. The role of routine biopsy of the background liver in the management of hepatocellular carcinoma.

Author

Lee S, Ahmed M, Taddei T, and Jain D

Subjects
Humans, Female, Middle Aged, Male, Liver Cirrhosis, Biopsy, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy
Abstract

We sought to determine the influence of background liver biopsies on hepatocellular carcinoma (HCC) management. The pathology database at a large university hospital was searched between 2013 and 2018 for all instances of when a separate biopsy of the nontumoral liver was performed within 6 months of an HCC biopsy. Patients were evaluated for baseline demographic and clinical characteristics, treatment proposed prior to biopsy, and impact of biopsy results on management. Among the 104 identified cases of paired liver biopsies, 22% were women; the median age was 64 years; and most were of earlier HCC stages at diagnosis (Barcelona Clinic Liver Cancer stages 0-A: 70%). Four patients among 10 in whom cirrhosis status was clinically unclear were confirmed to have cirrhosis on biopsy, and 4 patients did not have cirrhosis despite clinical suspicion. Treatment was altered by the background parenchymal findings for 5 patients (5%): management was less aggressive for 4 patients and more aggressive for 1 patient. A background liver biopsy can significantly impact the management of a small subset of HCC patients, especially those with early disease, and should be considered concurrently with the biopsy of the mass., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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46. Medications for alcohol use disorder improve survival in patients with hazardous drinking and alcohol-associated cirrhosis.

Author

Rabiee A, Mahmud N, Falker C, Garcia-Tsao G, Taddei T, and Kaplan DE

Subjects
Humans, Acamprosate therapeutic use, Naltrexone therapeutic use, Retrospective Studies, Liver Cirrhosis, Alcoholic, Liver Cirrhosis drug therapy, Alcoholism complications, Alcohol Deterrents adverse effects
Abstract

Background: Medications for alcohol use disorder (MAUD) are highly effective in achieving and maintaining abstinence in patients with alcohol use disorder (AUD). Our aim was to evaluate the effect of MAUD on all-cause mortality in patients with alcohol-associated cirrhosis and active alcohol use., Methods: This was a retrospective cohort study of patients with alcohol-associated cirrhosis and high-risk alcohol use disorder in the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) database. Propensity score matching for exposure to MAUD (acamprosate or naltrexone) within a year after cirrhosis diagnosis was performed to account for potential confounders, and the association between MAUD and all-cause mortality was subsequently evaluated using Cox regression analysis., Results: A total of 9131 patients were included, of whom 886 (9.7%) were exposed to MAUD (naltrexone: 520, acamprosate: 307, both medications: 59). The duration of MAUD exposure was >3 months in 345 patients (39%). The strongest positive predictor of MAUD prescription was an inpatient diagnosis code for AUD, followed by a concurrent diagnosis of depression; the strongest negative predictor was a history of cirrhosis decompensation. After propensity score matching (866 patients in each group) with excellent covariate balance (absolute standardized mean differences <0.1), MAUD exposure was associated with improved survival, with an HR of 0.80 relative to no MAUD exposure (95% CI: 0.67-0.97, p = 0.024)., Conclusion: MAUD are underutilized in patients with alcohol-associated cirrhosis with high-risk alcohol use behavior but are associated with improved survival after adjustment for confounders such as the severity of liver disease, age, and engagement in the healthcare system., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Published
2023
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47. Association between statin exposure and short-term mortality in patients with high-grade acute-on-chronic liver failure.

Author

Chapin S, Kaplan DE, Taddei T, and Mahmud N

Abstract

Background & Aims: Acute-on-chronic liver failure (ACLF) carries a high short-term mortality for patients with cirrhosis. Prior literature suggests that statin exposure may reduce the likelihood of ACLF events. However, it is unclear if statin exposure is associated with ACLF-related mortality. This study sought to determine the association between statin use and short-term mortality among patients hospitalised with ACLF., Methods: This was a retrospective cohort study of Veterans Health Administration (VHA) patients diagnosed with cirrhosis between 2008 and 2021 and hospitalised with high-grade (2 or 3) ACLF. Patients were stratified into those with and without continuous statin exposure for at least 90 days prior to hospitalisation. Multivariable logistic regression models were created to determine the adjusted association between statin exposure and 28-day and 90-day mortality. Categorical statin dose exposure, converted to simvastatin equivalents, was also explored., Results: A total of 11,731 patients with cirrhosis hospitalised with Grade 2 or 3 ACLF were included in the analytic cohort, 26% of whom had statin exposure. In adjusted logistic regression models, statin use was associated with 18% lower odds of ACLF-related 28-day mortality (odds ratio [OR] 0.82, 95% CI 0.73-0.93, p  = 0.001) and 24% lower odds of 90-day mortality (OR 0.76, 95% CI 0.68-0.86, p <0.001). Increasing statin dose exposure was also associated with further reductions in 90-day mortality ( e.g. OR 0.81, 95% CI 0.70-0.93 for 10-40 mg vs. 0 mg and OR 0.72, 95% CI 0.60-0.87 for 80 mg vs. 0 mg, p <0.001)., Conclusions: In this large, retrospective cohort study, statin exposure before high-grade ACLF hospitalisation was associated with reduced odds of 28-day and 90-day mortality in patients with cirrhosis. A statin dose-dependent reduction in 90-day ACLF-related mortality was also observed., Impact and Implications: Statins have been identified as a class of medications with potential beneficial effects for patients with cirrhosis. In this large, retrospective cohort study of patients with cirrhosis who seek care at the Veterans Health Administration, statin use was associated with a decrease in short term (28-day and 90-day) mortality as a result of acute-on-chronic liver failure. Future prospective studies are needed to further clarify the relative safety and efficacy of statin therapy in reducing morbidity and mortality associated with acute-on-chronic liver failure in patients with cirrhosis., Competing Interests: The authors have no additional disclosures or conflicts as relevant to this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Published
2023
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48. COVID-19 and the liver: a narrative review of the present state of knowledge.

Author

Thandassery RB, Dranoff JA, Perisetti A, and Taddei T

Abstract

Novel corona virus disease (COVID-19) is an ongoing pandemic that has spread across the globe. The virus primarily infects type-2 pneumocytes in alveoli and causes lung disease, with severity ranging from mild pneumonia to acute respiratory distress syndrome. The virus also invades gastrointestinal epithelial cells, hepatocytes, and biliary epithelial cells. Derangement of liver function tests is noted in about one third of patients and appears to correlate with more severe disease. There are multiple mechanisms by which the virus can cause liver injury; immune-mediated inflammation and direct viral cytotoxicity are believed to be the predominant mechanisms. Liver injury appears to be transient, usually recovering with resolution of illness. Limited available studies and experience from prior corona virus pandemics seem to suggest that immunosuppressed patients have similar outcomes compared to non-immunosuppressed patients. Age and comorbid conditions seem to influence outcome, irrespective of immune status. Additionally, patients with preexisting comorbid conditions are more prone to acquire infection and should strictly adhere to travel and social distancing advisories. Telemedicine should be utilized to provide uninterrupted care for patients with liver disease, and clinic or hospital visits should be advised only in sick patients with advanced liver disease. In conclusion, liver dysfunction is not uncommon in COVID-19, it generally improves with resolution of disease, and patients with chronic liver disease (CLD) need continued follow up, uninterrupted by the ongoing pandemic, preferably in virtual clinic settings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-20-243/coif). The authors have no conflicts of interest to declare., (2022 Translational Gastroenterology and Hepatology. All rights reserved.)

Published
2022
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50. Optimization of the BCLC Staging System for Locoregional Therapy for Hepatocellular Carcinoma by Using Quantitative Tumor Burden Imaging Biomarkers at MRI.

Author

Borde T, Nezami N, Laage Gaupp F, Savic LJ, Taddei T, Jaffe A, Strazzabosco M, Lin M, Duran R, Georgiades C, Hong K, and Chapiro J

Subjects
Biomarkers, Tumor, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Staging, Retrospective Studies, Treatment Outcome, Tumor Burden, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic, Liver Neoplasms diagnostic imaging, Liver Neoplasms therapy
Abstract

Background Patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC) represent a highly heterogeneous patient collective with substantial differences in overall survival. Purpose To evaluate enhancing tumor volume (ETV) and enhancing tumor burden (ETB) as new criteria within the Barcelona Clinic Liver Cancer (BCLC) staging system for optimized allocation of patients with intermediate- and advanced-stage HCC to undergo transarterial chemoembolization (TACE). Materials and Methods In this retrospective study, 682 patients with HCC who underwent conventional TACE or TACE with drug-eluting beads from January 2000 to December 2014 were evaluated. Quantitative three-dimensional analysis of contrast-enhanced MRI was performed to determine thresholds of ETV and ETB (ratio of ETV to normal liver volume). Patients with ETV below 65 cm 3 or ETB below 4% were reassigned to BCLC B n , whereas patients with ETV or ETB above the determined cutoffs were restratified or remained in BCLC C n by means of stepwise verification of the median overall survival (mOS). Results This study included 494 patients (median age, 62 years [IQR, 56-71 years]; 401 men). Originally, 123 patients were classified as BCLC B with mOS of 24.3 months (95% CI: 21.4, 32.9) and 371 patients as BCLC C with mOS of 11.9 months (95% CI: 10.5, 14.8). The mOS of all included patients (including the BCLC B and C groups) was 15 months (95% CI: 12.3, 17.2). A total of 152 patients with BCLC C tumors were restratified into a new BCLC B n class, in which the mOS was then 25.1 months (95% CI: 21.8, 29.7; P < .001). The mOS of the remaining patients (ie, BCLC C n group) ( n = 222; ETV ≥65 cm 3 or ETB ≥4%) was 8.4 months (95% CI: 6.1, 11.2). Conclusion Substratification of patients with intermediate- and advanced-stage hepatocellular carcinoma according to three-dimensional quantitative tumor burden identified patients with a survival benefit from transarterial chemoembolization before therapy. © RSNA, 2022 Online supplemental material is available for this article .

Published
2022
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