Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Evaluation Of Fluoride Content Of Bottled Drinking Waters In Brazil [avaliação Da Concentração De Flúor Em águas Minerais Comercializadas No Brasil]

The utilization of a systemic fluoride method must be controlled in terms of risks and benefits. The reason for this is that while a small dose will not be effective in preventing dental caries, a larger dose may cause dental fluorosis. Therefore the knowledge of the fluoride concentration found in the bottled mineral waters sold throughout the Brazilian market the consumption of which has increased lately, is of great concern. The objective of the study was the analysis of the concentration of fluoride found in the bottled mineral waters. A hundred and four brands coming from different regions of Brazil were analysed using an Orion 96-09 ion specific electrode and an Orion EA 940 ionanalyser, previously calibrated with standard fluoride solutions. Different concentrations of fluoride ranging from 0.0 to 4.4 were found. It was discovered that specific bottled waters contained: 1) Significant concentrations of fluoride not reported by the producer; 2) Fluoride concentrations of no preventive effect, although the producer had advertised the water as a Fluoridated Mineral Water; 3) Fluoride concentrations high enough to cause dental fluorosis, although the producer did not alert the consumer to this fact. It is to be concluded, therefore, that a sanitary regulatory system for the control of the level of fluoride in the bottled mineral waters marketed is necessary. Such reputation should be formulated in terms of benefits as well as in terms of risks.306512518Boivin, G., Chavassieux, P., Chapuy, M.C., Baud, C.A., Meunier, P.J., Profil histomorfophométrique de la fluorose osseuse induite par l'ingestion prolongée d'eau de Vichy Saint-Yorre (1986) Pathol. Biol., 34, pp. 33-39Leis e Decretos. Código de águas minerais: Decreto-Lei n. 7.841 de 08 de ago. 1945 (1945) Diário Oficial da União, p. 194. , 20 ago(1994) Sumário Mineral, 14. , Brasília(1991) Anuário Mineral Brasileiro, 20. , BrasíliaPortaria no 56 / Dsb - 14 mar. 1977 (1977) Diário Oficial da União, , 15 jun. Seção I - parte IBurt, B.A., The changing patterns of systemic fluoride intake (1992) J. Dent. Res., 71, pp. 1228-1237Capella, L.F., Carcereri, D.L., Paiva, S.M., Rosso, R.A., Paixão, R.F., Saltori, E.K., Freitas, A.R.R., Barros Filho, M.A., Ocorrência de fluorose dental endêmica (1989) Rev. Goian. Odont., 37, pp. 371-375Chan, J.T., Stark, C., Jeske, A.H., Fluoride content of bottled waters: Implications for dietary fluoride supplementation (1990) Tex. Dent. J., 107, pp. 17-21Clovis, J., Hargreaves, J.A., Fluoride intake from beverage consumption (1988) Community Dent. Oral Epidemiol., 16, pp. 11-15Dillenberg, J.S., Levy, S.M., Schoroeder, D.C., Gerston, E.N., Andersen, C.J.C., Arizona providers' use and knowledge of supplements (1992) Clin. Prev. Dent., 14, pp. 15-26Ellwood, R.P., Côrtes, D.F., O'Mullane, D.M., Fluoride exposure and enamel defects in Brazil (1994) J. Dent. Res., 73, p. 331Evans, R.W., Stamm, J.W., An epidemiologic estimate of the critical period during which human maxillary central incisors are most susceptible to fluorosis (1991) J. Public Health Dent., 51, pp. 251-259Flaitz, C.M., Hill, E.M., Hicks, M.J., A survey of bottled water usage by pediatric dental patients : Implications for dental health (1989) Quintessence Int., 20, pp. 847-852Franco, F.C., Maltz, M., A concentração de fluoretos em águas minerais, chás brasileiros e chimarrão (1991) Anais, p. 4. , Reunião da Sociedade Brasileira de Pesquisas Odontológicas, 8. Águas de São PedroJasmin, J.R., Ionesco-Benaiche, N., Muller, M., Latent fluorides: Report of case (1995) J. Dent. Child., 62, pp. 220-223Jones, K.F., Berg, J.H., Fluoride supplementation: A survey of pediatricians and pediatric dentists (1992) Am. J. Dis. Child., 146, pp. 1449-1491Kuthy, R.A., Mc Tigue, D.J., Fluoride prescription practices of Ohio physicians (1987) J. Public. Health Dent., 47, pp. 172-176Lalumandier, J.A., Rozier, R.G., The prevalence and risk factors of fluorosis among patient in a pediatric dental practice (1995) Pediatr. Dent., 17, pp. 19-24Lantz, O., Jouvin, M.H., De Vernejoul, M.C., Druet, P., Fluoride induced chronic renal failure (1987) Am. J. Kidney Dis., 10, pp. 136-139Larsen, M.J., Richards, A., Fejerskov, O., Development of dental fluorosis according to age at start of fluoride administration (1985) Caries Res., 19, pp. 519-527Levy, S.M., Systemic fluoride supplementation in an academic family practice setting (1987) J. Fam. Pract., 24, pp. 532-536Levy, S.M., Kiristy, M.C., Warren, J.J., Sources of fluoride intake in children (1995) J. Public. Health Dent., 55, pp. 39-52Levy, S.M., Maurice, T.J., Jakobsen, J.A., Feeding patterns, water sources and fluoride exposures of infants and 1-year-olds (1993) J. Am. Dent. Assoc., 124, pp. 65-69Mac Fayden, E.E., McNee, S.G., Weetman, D.A., Fluoride content of some bottled spring waters (1982) Br. Dent. J., 153, pp. 423-424Margolis, F.J., Burt, B.A., Schork, M.A., Bashshur, H.L., Whittaker, B.A., Burns, T.L., Fluoride supplements for children (1980) Am. J. Dis. Child., 134, pp. 865-868McGuire, S., Fluoride content of bottled water (1989) N. Engl. J. Med., 321, pp. 836-837Meunier, P.J., Femenias, M., Duboeuf, F., Chapuy, M.C., Delmas, P.D., Increased vertebral bone density in heavy drinkers of mineral water rich in fluoride (1989) Lancet, 1, p. 152Sampaio, F.C., Bezerra, R., Dental fluorosis in Paraiba- Brazil. An epidemiological survey in geomedical interactins (1995) Abstracts of Papers, p. 46. , World Congress on Preventive Dentistry, 5. São Paulo, 1995. São PauloSchalka, M.M.S., Rodrigues, C.R.M.D., A importância do médico pediatra na promoção da saúde bucal (1996) Rev. Saúde Pública, 30, pp. 179-186Soviero, V.M., Massao, J.M., Ramos, M.E., Tura, L.F., Posicionamento dos médicos pediatras frente a questões de odontopediatria (1995) Anais, p. 123. , Reunião da Sociedade Brasileira de Pesquisas Odontológicas, 12. Águas de São Pedro, 1995Stannard, J., Rovero, J., Tsamtsouris, A., Gavris, V., Fluoride content of some bottled waters and recommendations for fluoride supplementation (1990) J. Pedod., 14, pp. 103-107Tate, W.H., Snyder, R., Montgomery, E.H., Chan, J.T., Impact of source of drinking water on fluoride supplementation (1990) J. Pediatr., 117, pp. 419-421Toumba, K.J., Levy, S., Curzon, M.E.J., The fluoride content of bottled drinking waters (1994) Br. Dent. J., 176, pp. 266-2681986. apud Newbrun, E. Current regulations and recommendations concerning water fluoridation, fluoride supplements, and topical fluoride agents (1992) J. Dent. Res., 71, pp. 1255-1265Van Winkle, S., Levy, S.M., Kiritsy, M.C., Heilman, J.R., Wefel, J.S., Marshall, T., Water and formula fluoride concentrations: Significance for infants fed formula (1995) Pediatr. Dent., 17, pp. 305-310Weinberger, S.J., Bottled drinking waters: Are the fluoride concentrations shown on the labels accurate? (1991) Int. J. Paed. Dent., 1, pp. 143-1461984. apud Newbrun, E. Current regulations and recommendations concerning water fluoridation, fluoride supplements, and topical fluoride agents (1992) J. Dent. Res., 71, pp. 1255-126

Spatial distribution of soil contaminated with Toxoplasma gondii oocysts in relation to the distribution and use of domestic cat defecation sites on dairy farms

International audienc

Highly hydrophobic wood surfaces prepared by treatment with atmospheric pressure dielectric barrier discharges

We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes. " 2006 The Authors.",,,,,,"10.1111/j.1399-0039.2006.00636.x",,,"http://hdl.handle.net/20.500.12104/41926","http://www.scopus.com/inward/record.url?eid=2-s2.0-33747198504&partnerID=40&md5=708deb2f425261c7da37e7db2c2e017f",,,,,,"2",,"Tissue Antigens",,"13

High-resolution molecular characterization of the HLA class I and class II in the Tarahumara Amerindian population

We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes. © 2006 The Authors