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1. Genetics and epidemiology of UGT1A1 and serum bilirubin levels

Author

Horsfall, L. J., Swallow, D., and Pereira, S.

Subjects
615.5
Abstract

The UGT1A gene complex encodes nine enzymes responsible for converting endogenous molecules such as bilirubin and a range of drugs to soluble glururonides for physiological elimination. Reduced UGT1A1 activity, mainly due to a promoter variant, UGT1A1 *28, underlies mild hereditary hyperbilirubinaemia (a familial jaundice known as Gilbert‟s syndrome) and deficiencies of UGT1A1 and the other UGT1A isoforms may increase risk of adverse drug reactions (ADRs). On the other hand moderately raised bilirubin levels appear to protect against cardiovascular disease in humans, which is purportedly due to the potent antioxidant properties of serum bilirubin. The major aims of this thesis were to: 1) report the prevalence of Gilbert‟s syndrome recorded in GP practices in the UK and identify factors associated with clinical recognition, 2) evaluate the association between bilirubin levels and respiratory diseases, 3) examine the influence of UGT1A1 variants on cardiovascular risk factors, lung function and neonatal jaundice, 4) compare the prevalence of clinically relevant genotypes and haplotypes of the UGT1A gene complex in different human populations. The main findings were: although around 5% of the primary care sample with bilirubin levels recorded had a phenotype consistent with Gilbert‟s syndrome, only 4% of these patients had a medical record of the condition, and factors other than genetics, in particular gender, smoking status, social deprivation and time period can influence clinical diagnosis. In a cohort of over half a million UK primary care patients with bilirubin levels recorded but with no evidence of hepatobiliary disease, each 1.7μmol/L (0.1mg/dL) increase in bilirubin was independently associated with an 8% decrease (95%CI; 5-11%) for males and an 11% decrease (95%CI; 7-14%) for females in the incidence of lung cancer. Each 1.7μmol/L increase in bilirubin was associated with a 6% decrease (95%CI; 5-7%) in COPD and a 3% decrease (95%CI; 2-3%) in mortality for males. The results for COPD and mortality in females were very similar. The UGT1A1*28 allele was not associated with neonatal jaundice, blood pressure or cholesterol levels in a cohort of 2,691 people from the UK followed since birth in 1946. However, there was an association with lung function. Cardiovascular events will be important to study when available. While around 10% of a UK population is homozygous for UGT1A1 *28, the allele frequency was even higher in equatorial African regions. But haplotype diversity was much greater than in Europe where the low activity alleles of the UGT1A gene complex are in most cases present on the same haplotype. These population differences have important implications for pharmacogenetic diagnostics such as those approved for use in the USA.

Published
2011

2. Stereoselective synthesis of pyrrolidinones via nitro-Mannich reaction : towards the synthesis of popolohuanone E

Author

Horsfall, L. R.

Subjects
540
Abstract

Part 1: The first section of this thesis details the stereoselective synthesis of pyrrolidinones via the nitro-Mannich reaction. Expanding on previous work within the Anderson group, conjugate addition of a diorganozinc species to nitroacrylate 141 was carried out successfully. Subsequent in situ nitro-Mannich reaction was then followed by spontaneous lactamisation to afford the desired five-membered ring pyrrolidinone structure. The reaction was performed in one pot, generating three contiguous stereocentres in a highly diastereoselective manner. The scope of the reaction was investigated by varying substituents on the imine partner. This led to the synthesis of a broad range of analogues incorporating alkyl, aryl and heteroaryl functional groups, each isolated as a single diastereoisomer in 48-84% yield. Studies to develop an asymmetric variant of the reaction were performed, with Feringa’s phosphoramidite ligand 299 enabling formation of the pyrrolidinone with a moderate 52% e.e. Analysis of the reaction mechanism and the origin of the observed diastereoselectivity have been investigated, followed by further functionalisation of the pyrrolidinone structure to yield a wide range of synthetically useful building blocks. Anderson, J. C.; Stepney, G. J.; Mills, M. R.; Horsfall, L. R.; Blake, A. J.; Lewis, W. J. Org. Chem. 2011, 76, 1961 (featured article). Part 2: This section describes work towards the total synthesis of popolohuanone E (1), a marine natural product isolated from the Dysidea sp. sponge in 1990. The molecule contains a unique trihydroxylated dibenzofuran-1,4-dione core and two identical sesquiterpene units. The complex molecular structure and interesting biological activity of popolohuanone E (1) has made this compound a particularly interesting target. Synthesis of model system 132 was successfully achieved, which allowed investigations into the key oxidative dimerisation reaction. Extensive studies led to isolation of the desired bis-quinone 133 in 40% yield, followed by acid catalysed cyclisation to form the dibenzofuran core present in popolohuanone E (1), in 26% yield. Focus then turned to the synthesis of the proposed precursor to popolohuanone E (1), 6’-hydroxyarenarol (7), based on the route developed within the Anderson group. Studies began with the enantioselective synthesis of intermediate iodide 83 utilising Myers’ pseudo-ephedrine auxillary. The remaining stereocentres were subsequently installed via an intramolecular Hosomi-Sakurai reaction in high yield and diastereoselectivity. With the cis-decalin framework in hand, construction of the phenolic portion was achieved by addition of lithiated 1,2,4-trimethoxybenzene to neo-pentyl aldehyde 74, followed by deoxygenation using Barton-McCombie conditions. Installation of the exo-cyclic alkene, followed by removal of the three methyl ether protecting groups, then afforded the required precursor 6’- hydroxyarenarol (7). Finally, dimerisation was attempted as developed previously on model system 132, however none of the desired bis-quinone (18) was observed.

Published
2011

25. RNA-sequencing analysis of biopsies from chronic liver disease patients identifies gene signatures associated with progressive liver disease

Author

Ramnath, D., primary, Irvine, K., additional, Lukowski, S., additional, Horsfall, L., additional, Loh, K., additional, Clouston, A., additional, Patel, P., additional, Iyer, A., additional, Lampe, G., additional, Stow, J., additional, Schroder, K., additional, Fairlie, D., additional, Powell, J., additional, Powell, E., additional, and Sweet, M., additional

Published
2018
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26. Vorapaxar in the secondary prevention of atherothrombotic events

Author

Braunwald E, Morrow DA, Scirica BM, Bonaca MP, McCabe CH, Morin S, Fish P, Lamp J, Gershman E, Murphy S, Deenadayalu N, Skene A, Hill K, Bennett L, Strony J, Plat F, Berman G, Lipka L, Kilian A, He W, Liu X, Fox KA, Aylward P, Bassand JP, Betriu A, Bounameaux H, Corbalan R, Creager M, Dalby A, De Ferrari G, Dellborg M, Diehm CH, Dietz R, Goto S, Grande P, Gurbel P, Hankey G, Isaza D, Jensen P, Kiss R, Lewis B, Merlini P, Moliterno D, Morais J, Nicolau JC, Nieminen M, Nilsen D, Olin J, Ophuis TO, Paolasso E, Pichler M, Shinohara Y, Spinar J, Teal P, Tendera M, Theroux P, Thomassen L, Van de Werf F, White H, Wilcox R, Alberts M, Ameriso S, Diener H, Mohr J, Welch M, Wiviott SD, Awtry E, Berger C, Desai A, Gelfand E, Ho C, Leeman D, Link M, Norden A, Pande A, Rost N, Ruberg R, Silverman S, Singhal A, Vita J, Frye RL, Bailey KR, Easton J, Hochman J, Steg PG, Verheught F, Lee K, Mauro DO, Centurion A, Carlevaro O, Cardozo E, Cartasegna L, Soccini N, Farras HA, Molina Aguirre E, Duronto E, Arrechavala L, Rey R, Stilman A, Fernández H, Marinsalta G, Tartaglione J, Chekherdemian M, Povedano G, Casares E, Kantor P, Reges P, Cuneo C, Martinez G, MacKinnon I, Bagnato B, Fernandez A, Funosas C, Lozada A, Barilati P, Ferrari J, Ferrari N, Llanos J, Casaccia G, Giannaula R, García Méndez C, Cirio J, García Dávila C, Estol C, Chiezzo D, Ramirez J, Garrido S, López M, Hominal M, Bianchini MV, Ramos M, Verdini E, Herrera G, Monne H, Ioli P, Samudio MA, Rotta Escalante R, Tarulla A, Reich E, Perez G, Milesi R, Berli M, Marino J, Funes I, Prado A, Bezi M, Fernandez R, Rojas M, Cimbaro Canella JP, Galarza Salazan M, Chew D, Horsfall L, Claxton A, French J, O'Brien K, Nelson G, Loxton A, McCann A, Downey C, Aroney C, Cleave P, Worthley S, Roach A, Amerena J, Long A, Thompson P, Ferguson L, Fitzpatrick M, Mackenzie M, Youssef G, Goldsmith H, Jayasinghe R, Quinlan S, Arstall M, Rose J, Counsell J, Martin M, Crimmins D, Slattery A, Anderson C, Paraskevaidis T, Davis S, Silver G, Gerraty RP, Gapper J, Donnan G, Petrolo S, Whelan A, Tulloch G, Singh B, Campo Ma, Dick R, Savage C, Hill A, Conway B, Waites J, Keays P, Kopp K, Hainzer D, Podczeck Schweighofer A, Priesnitz T, Drexel H, Hagspiel V, Foeger B, Hilbe C, Trinka E, Sinadinoska D, Pilger E, Brodmann M, Stöllberger C, Jungbauer LV, Koppensteiner R, Hoke M, Grisold W, Berger O, Gaul GB, Fazekas N, Wandaller C, Stockenhuber F, Rek A, Willeit J, Zangerle A, Kiechl S, Sturm W, Theurl M, Gruber F, Schacherl S, Auer J, Primus C, Eber B, Ammer M, Hofer JF, Mayr H, Moser S, Hoellmueller I, Van der Werf F, Motte S, Jorion M, Schroë H, Zwinnen W, Vermassen F, Geenens M, De Wolf L, Briké C, De Deyn P, Ongena P, De Klippel N, Meeuwissen K, Desfontaines P, Tincani G, Vandermeeren Y, de Fays K, Pandolfo M, Alaerts N, Peeters A, Findik A, Tack P, deGrande E, Thijs V, Marcelis E, Van Landegem W, Vanhagendoren S, Vanhooren G, Schotte V, Celen H, Bes N, De Letter J, Holvoet G, Claerbout B, Verhamme P, Debaveye B, Bourgeois P, Debrabandere K, Stalpaert S, Dhondt E, De Maeseneire S, De Bleecker J, de Koning K, Vincent M, Tahon S, Monté C, Maes J, Vossaert R, Vandenhoven C, Roosen J, Vissers C, Sinnaeve P, de Velder L, Thoeng J, Cauwenberghs J, Deceuninck F, Nicolau J, Ardito WR, Queirantes C, de Araujo Filho JD, Queirantes CS, Ribeiro JP, Guizzardi SP, Chaves ML, Titton NF, Pereira AH, Webber I, da Silva DG Jr, Uehara RM, Brasileiro J, Maia LN, Souza A, Bodanese LC, Homem R, Friedrich MA, Macagnan AP, Dutra OP, Brum AB, Rossi PR, Herek L, Feitosa GS, Bernardes Ade S, Braga J, Rodrigues D, Guimarães A, Teixeira AB, Marin Neto JA, Tonani M, Piegas LS, Amato V, Leães P, Osorio RL, Ganem F, Vieira AP, Leao P, Kanashiro V, Franken RA, Martins EP, Gagliardi RJ, Silva L, Caffaro RA, Novaes GS, Carvalho A, Laet VL, Miranda F. Jr, Crippa BA, Saraiva JF, Ormundo CT, Speciali JG, Guandolini G, de Albuquerque DC, Silva V, Abrantes JA, Pinheiro L, Teixeira MS, Guanaes DF, Resende ES, Andrade SF, Alves ÁR Jr, Oliveira OM, Tauil CB, Araujo E, de Souza J, de Freitas GR, Horokosky AP, Barbosa EC, Muniz P, de Moraes JB Jr, Cabral M, Faria Neto JR, Belemer A, Paiva MS, Brito A, Hernandes ME, Amorim R, Pittella FJ, Brito HH, Kouz S, Roy M, Gosselin G, David M, Huynh T, Boudreault C, Heath J, Scott L, Bhargava R, Stafford C, Klinke WP, Martin L, Chan YK, Zaniol D, Rebane T, Abramovich M, Vizel S, Fox B, Kornder J, Breakwell L, Constance C, Gauthier M, Cleveland D, Valley S, Dion D, Morissette A, Vertes G, Ross B, Pandey AS, Byrne M, Abramson B, Sodhi N, Ervin F, Thiessen S, Halperin F, Stedham V, Pesant Y, Sardin V, Saw J, Tarry L, Pouliot J, Marquette S, Belisle P, Gagne D, Ducas J, Munoz A, Sussex B, Newman S, Madan M, Hsu E, Bata I, Cossett J, Glanz A, Vilag C, Paddock V, Collings E, Sabbah E, Chausse I, Fortin C, Lepage C, Chehayeb R, Viau C, Ma P, Seib M, Lamy A, Rizzo A, Rajakumar AR, Eikel L, Nigro F, Stoger S, Welsh R, Lindholm L, Parker JD, Webber S, Winkler L, Hannah G, Gupta M, Kubiak A, Mukherjee A, Bozek B, Nguyen M, Dufort L, Haichin R, Toyota V, Bujold S, Syan G, Chinnasane S, Houde G, Rousseau S, Poirier P, Lariviere M, Dupuis R, Ouimet F, Audet J, Darveau C, Labonte R, Rice T, Nawaz S, Cantor W, Robbins K, Boucher P. Jr, Roberge J, Zadra R, McPherson C, Prieto JC, Noriega V, Cereño C, Mestas M, Yovaniniz P, Ferrada W, Pincetti C, Torres G, Perez L, Villan C, Escobar E, Martin R, Padilla I, Ramirez M, Hormazabal R, Pedemonte O, Suazo E, Hasbun S, Mejias M, Cardenas F, Donoso L, Godoy I, Henriquez P, Mariné L, Vergara T, Juri C, Vergara E, Muñoz M, Solano E, Toro J, Cardenas S, Mendoza F, Martinez S, Saaibi JF, Castillo KM, Ruiz NP, Castillo T, Orozco A, Muñoz C, Martínez J, Lopez D, Ochoa J, Andrade J, Jaramillo C, Garces GP, Botero R, Cáceres A, Jaramillo M, Mejia C, Schlesinger A, Munevar V, Rodriguez J, Granados LM, Jaramillo N, Aristizabal C, Cano N, Salazar JC, Urina M, Manco T, Valenzuela C, Hernandez HJ, Delgado PS, Vagner B, Castaño LA, Ucros P, Tellez M, Delgado JA, Piedrahita CA, Crump J, Fernandez V, Quintero CA, Moreno M, Hernandez Triana E, Cuentas I, Accini JL, Accini M, Manzur F, Rivera E, Reynales H, Huertas D, Hovorka J, Filipovsky J, Hirmerova J, Peska S, Jura R, Kanovsky P, Herzig R, Jansky P, Fiala R, Kalita Z, Gatkova A, Bauer J, Fiksa J, Sedlacek J, Monhart Z, Bren J, Linhart A, Skalicka L, Vitovec J, Hlinomaz O, Parenica J, Soucek M, Rihacek I, Branny M, Sknouril L, Klimsa Z, Holub M, Línkova H, Rektor I, Mikulik R, Mayer O. Sr, Novakova B, Bar M, Brodova P, Polasek R, Sabl P, Kos P, Lorenc Z, Macel I, Graversen KH, Galatius S, Soderberg LH, Sillesen H, Madelung S, Overgård K, Stan V, Rasmussen LH, Mortensen B, Iversen HK, Back C, Olesen C, Christensen H, Pedersen A, Nielsen T, Hasain M, Tanggaard L, Husted S, Christensen LL, Haas L, Mickley H, Hosbond S, Rosenlund I, Jepsen J, Kaspersen BB, Bronnum Schou J, Hempel H, Nyvad O, Feldthaus B, Jensen BS, Jensen MK, Andersen G, Thomsen RB, Rokkedal J, Joergensen A, Bülow M, Jeppesen J, Lederballe O, Scheibel I, Sjol A, Larsen J, Graner M, Svahn T, Melin J, Kaakkomäki A, Airaksinen J, Vasankari T, Tatlisumak T, Metso M, Remes A, Näppä M, Jäkälä P, Sivenius J, Kalinen M, Roine RO, Ketola R, Bassand J, Pales D, Coisne D, Berger N, Galinier M, Rosolin N, Elbaz M, Lacassagne L, Montalescot G, Vignolles N, Gully C, Lepage I, Roynard J, Hamon M, Brucato S, Macquin Mavier I, Beitar T, Berthezene P, Medkour T, Amarenco P, Gueblaoui N, Timsit S, Riou D, Mahagne M, Suissa L, Quere I, Clouzot S, Emmerich J, Martinez I, Moulin T, Cole M, Hosseini H, Monod V, Cottin Y, Bichat F, Galley D, Beltra C, Samson Y, Pires R, Bura Riviere A, Pelvet B, Giroud M, Lecheneaut C, Ohlmann P, Ait m. bark Z, Farah B, Petit F, Caussin C, Braun C, Diehm C, Mehrhof F, Inkrot S, Darius H, Heinze H, Radke P, Kulikowsky C, Ferrari M, Utschig S, Strasser R, Haacke K, Felix SB, Bruder M, Nienaber C, Pfaff H, Sohn H, Baylacher M, Mudra H, Setzer P, Konstantinides S, Hallmann A, Kreuzer J, Tsoy I, Schneider P, Appel KF, Habermeier A, Zeiher AM, Kretschmer T, Mitrovic V, Lehinant S, Bohlscheid V, Palme B, Heuer H, Espinola Klein C, Savvidis S, Kleinertz K, Hänel J, Schmidt E, Schmidt A, Ringleb PA, Ludwig I, Dietzold M, Schaffranka A, Ranft J, Cegla C, Berrouschot J, Stoll A, Tanislav C, Brandtner MA, Rosenkranz M, Otto D, Görtler M, Barleben M, Haberl R, Miedl S, Maschke M, Schröder K, Aral Becher B, Herzog Hauff S, Guenther A, Herzau C, Hoffmann U, Roth Zetzsche S, Grond M, Becker M, Hamann G, Simon K, Köhrmann M, Glahn J, Wuttig H, Nabavi DG, Seraphin D, Schellong S, Frommhold R, Dichgans M, Doerr A, Blessing E, Buss I, Butter C, Bettin D, Grosch B, Blank E, Wong L, Liu R, Lee S, Kong S, Yu C, So E, Jakal Á, Masszi G, Czuriga I, Kapocsi J, Soós E, Csiba L, Fekete K, Valikovics A, Dioszeghy P, Muskóczki E, Csányi A, Matoltsy A, Yuval R, Bornstein N, Elimelech R, Chajek Shaul T, Bursztyn M, Hayek T, Hazbon K, Gavish D, Anat N, Wexler D, Azar P, Mosseri M, Tsirulnikov E, Rozenman Y, Logvinenko S, Tanne D, Don A, Gross B, Feldman Y, Klainman E, Genin Dmitrishin I, Eldar M, Eizenberg N, Atar S, Lasri E, Hammerman H, Aharoni G, Zimlichman R, Zuker S, Telman G, Afanasiev S, Katz A, Biton A, Goldhaber A, Goldhaber M, Elian D, Linor A, Meyuhas S, Tsalihin D, Kissos D, Lampl Y, Israelson M, Gottlieb S, Dotan L, Elis A, Karny M, Hussein O, Shestatski K, Brenner H, Segal E, Baldini U, Gavazzi A, Poloni M, Censori B, Aiazzi L, Maraglino C, Marenzi G, Specchia G, Tritto I, Golino P, CIANFLONE , DOMENICO, Martignoni A, Tamburino C, Rubartelli P, Ardissino D, Tadonio I, Stramba Badiale M, Cernuschi P, Nardulli R, Sommariva L, Giordano A, Berni A, Cavallini C, Fiscella A, Azzarelli S, Esposito G, Cassese S, Danzi G, Fattore L, Barbieri E, De Caterina R, Odero A, Puttini M, Corrada E, Monzini N, Vadalà A, Pistarini C, Scrutinio D, Ferratini M, Marcheselli S, Moretti L, Partemi L, Pupilella T, Lazzari A, Ledda A, Geraci G, Rasura M, Beccia M, Cassadonte F, Vatrano M, Bongiorni D, Mos L, Marcuzzi G, Murena E, Uguccioni L, Ferretti C, Piti ATerrosu P, Perrone PF, Marconi R, Grasso L, Severi S, Evola R, Russo N, Agnelli G, Paci C, Carugo S, Silvestri O, Testa R, Novo S., Braunwald, E, Morrow, Da, Scirica, Bm, Bonaca, Mp, Mccabe, Ch, Morin, S, Fish, P, Lamp, J, Gershman, E, Murphy, S, Deenadayalu, N, Skene, A, Hill, K, Bennett, L, Strony, J, Plat, F, Berman, G, Lipka, L, Kilian, A, He, W, Liu, X, Fox, Ka, Aylward, P, Bassand, Jp, Betriu, A, Bounameaux, H, Corbalan, R, Creager, M, Dalby, A, De Ferrari, G, Dellborg, M, Diehm, Ch, Dietz, R, Goto, S, Grande, P, Gurbel, P, Hankey, G, Isaza, D, Jensen, P, Kiss, R, Lewis, B, Merlini, P, Moliterno, D, Morais, J, Nicolau, Jc, Nieminen, M, Nilsen, D, Olin, J, Ophuis, To, Paolasso, E, Pichler, M, Shinohara, Y, Spinar, J, Teal, P, Tendera, M, Theroux, P, Thomassen, L, Van de Werf, F, White, H, Wilcox, R, Alberts, M, Ameriso, S, Diener, H, Mohr, J, Welch, M, Wiviott, Sd, Awtry, E, Berger, C, Desai, A, Gelfand, E, Ho, C, Leeman, D, Link, M, Norden, A, Pande, A, Rost, N, Ruberg, R, Silverman, S, Singhal, A, Vita, J, Frye, Rl, Bailey, Kr, Easton, J, Hochman, J, Steg, Pg, Verheught, F, Lee, K, Mauro, Do, Centurion, A, Carlevaro, O, Cardozo, E, Cartasegna, L, Soccini, N, Farras, Ha, Molina Aguirre, E, Duronto, E, Arrechavala, L, Rey, R, Stilman, A, Fernández, H, Marinsalta, G, Tartaglione, J, Chekherdemian, M, Povedano, G, Casares, E, Kantor, P, Reges, P, Cuneo, C, Martinez, G, Mackinnon, I, Bagnato, B, Fernandez, A, Funosas, C, Lozada, A, Barilati, P, Ferrari, J, Ferrari, N, Llanos, J, Casaccia, G, Giannaula, R, García Méndez, C, Cirio, J, García Dávila, C, Estol, C, Chiezzo, D, Ramirez, J, Garrido, S, López, M, Hominal, M, Bianchini, Mv, Ramos, M, Verdini, E, Herrera, G, Monne, H, Ioli, P, Samudio, Ma, Rotta Escalante, R, Tarulla, A, Reich, E, Perez, G, Milesi, R, Berli, M, Marino, J, Funes, I, Prado, A, Bezi, M, Fernandez, R, Rojas, M, Cimbaro Canella, Jp, Galarza Salazan, M, Chew, D, Horsfall, L, Claxton, A, French, J, O'Brien, K, Nelson, G, Loxton, A, Mccann, A, Downey, C, Aroney, C, Cleave, P, Worthley, S, Roach, A, Amerena, J, Long, A, Thompson, P, Ferguson, L, Fitzpatrick, M, Mackenzie, M, Youssef, G, Goldsmith, H, Jayasinghe, R, Quinlan, S, Arstall, M, Rose, J, Counsell, J, Martin, M, Crimmins, D, Slattery, A, Anderson, C, Paraskevaidis, T, Davis, S, Silver, G, Gerraty, Rp, Gapper, J, Donnan, G, Petrolo, S, Whelan, A, Tulloch, G, Singh, B, Campo, Ma, Dick, R, Savage, C, Hill, A, Conway, B, Waites, J, Keays, P, Kopp, K, Hainzer, D, Podczeck Schweighofer, A, Priesnitz, T, Drexel, H, Hagspiel, V, Foeger, B, Hilbe, C, Trinka, E, Sinadinoska, D, Pilger, E, Brodmann, M, Stöllberger, C, Jungbauer, Lv, Koppensteiner, R, Hoke, M, Grisold, W, Berger, O, Gaul, Gb, Fazekas, N, Wandaller, C, Stockenhuber, F, Rek, A, Willeit, J, Zangerle, A, Kiechl, S, Sturm, W, Theurl, M, Gruber, F, Schacherl, S, Auer, J, Primus, C, Eber, B, Ammer, M, Hofer, Jf, Mayr, H, Moser, S, Hoellmueller, I, Van der Werf, F, Motte, S, Jorion, M, Schroë, H, Zwinnen, W, Vermassen, F, Geenens, M, De Wolf, L, Briké, C, De Deyn, P, Ongena, P, De Klippel, N, Meeuwissen, K, Desfontaines, P, Tincani, G, Vandermeeren, Y, de Fays, K, Pandolfo, M, Alaerts, N, Peeters, A, Findik, A, Tack, P, Degrande, E, Thijs, V, Marcelis, E, Van Landegem, W, Vanhagendoren, S, Vanhooren, G, Schotte, V, Celen, H, Bes, N, De Letter, J, Holvoet, G, Claerbout, B, Verhamme, P, Debaveye, B, Bourgeois, P, Debrabandere, K, Stalpaert, S, Dhondt, E, De Maeseneire, S, De Bleecker, J, de Koning, K, Vincent, M, Tahon, S, Monté, C, Maes, J, Vossaert, R, Vandenhoven, C, Roosen, J, Vissers, C, Sinnaeve, P, de Velder, L, Thoeng, J, Cauwenberghs, J, Deceuninck, F, Nicolau, J, Ardito, Wr, Queirantes, C, de Araujo Filho, Jd, Ribeiro, Jp, Guizzardi, Sp, Chaves, Ml, Titton, Nf, Pereira, Ah, Webber, I, da Silva DG, Jr, Uehara, Rm, Brasileiro, J, Maia, Ln, Souza, A, Bodanese, Lc, Homem, R, Friedrich, Ma, Macagnan, Ap, Dutra, Op, Brum, Ab, Rossi, Pr, Herek, L, Feitosa, G, Bernardes Ade, S, Braga, J, Rodrigues, D, Guimarães, A, Teixeira, Ab, Marin Neto, Ja, Tonani, M, Piegas, L, Amato, V, Leães, P, Osorio, Rl, Ganem, F, Vieira, Ap, Leao, P, Kanashiro, V, Franken, Ra, Martins, Ep, Gagliardi, Rj, Silva, L, Caffaro, Ra, Novaes, G, Carvalho, A, Laet, Vl, Miranda F., Jr, Crippa, Ba, Saraiva, Jf, Ormundo, Ct, Speciali, Jg, Guandolini, G, de Albuquerque, Dc, Silva, V, Abrantes, Ja, Pinheiro, L, Teixeira, M, Guanaes, Df, Resende, E, Andrade, Sf, Alves ÁR, Jr, Oliveira, Om, Tauil, Cb, Araujo, E, de Souza, J, de Freitas, Gr, Horokosky, Ap, Barbosa, Ec, Muniz, P, de Moraes JB, Jr, Cabral, M, Faria Neto, Jr, Belemer, A, Paiva, M, Brito, A, Hernandes, Me, Amorim, R, Pittella, Fj, Brito, Hh, Kouz, S, Roy, M, Gosselin, G, David, M, Huynh, T, Boudreault, C, Heath, J, Scott, L, Bhargava, R, Stafford, C, Klinke, Wp, Martin, L, Chan, Yk, Zaniol, D, Rebane, T, Abramovich, M, Vizel, S, Fox, B, Kornder, J, Breakwell, L, Constance, C, Gauthier, M, Cleveland, D, Valley, S, Dion, D, Morissette, A, Vertes, G, Ross, B, Pandey, A, Byrne, M, Abramson, B, Sodhi, N, Ervin, F, Thiessen, S, Halperin, F, Stedham, V, Pesant, Y, Sardin, V, Saw, J, Tarry, L, Pouliot, J, Marquette, S, Belisle, P, Gagne, D, Ducas, J, Munoz, A, Sussex, B, Newman, S, Madan, M, Hsu, E, Bata, I, Cossett, J, Glanz, A, Vilag, C, Paddock, V, Collings, E, Sabbah, E, Chausse, I, Fortin, C, Lepage, C, Chehayeb, R, Viau, C, Ma, P, Seib, M, Lamy, A, Rizzo, A, Rajakumar, Ar, Eikel, L, Nigro, F, Stoger, S, Welsh, R, Lindholm, L, Parker, Jd, Webber, S, Winkler, L, Hannah, G, Gupta, M, Kubiak, A, Mukherjee, A, Bozek, B, Nguyen, M, Dufort, L, Haichin, R, Toyota, V, Bujold, S, Syan, G, Chinnasane, S, Houde, G, Rousseau, S, Poirier, P, Lariviere, M, Dupuis, R, Ouimet, F, Audet, J, Darveau, C, Labonte, R, Rice, T, Nawaz, S, Cantor, W, Robbins, K, Boucher P., Jr, Roberge, J, Zadra, R, Mcpherson, C, Prieto, Jc, Noriega, V, Cereño, C, Mestas, M, Yovaniniz, P, Ferrada, W, Pincetti, C, Torres, G, Perez, L, Villan, C, Escobar, E, Martin, R, Padilla, I, Ramirez, M, Hormazabal, R, Pedemonte, O, Suazo, E, Hasbun, S, Mejias, M, Cardenas, F, Donoso, L, Godoy, I, Henriquez, P, Mariné, L, Vergara, T, Juri, C, Vergara, E, Muñoz, M, Solano, E, Toro, J, Cardenas, S, Mendoza, F, Martinez, S, Saaibi, Jf, Castillo, Km, Ruiz, Np, Castillo, T, Orozco, A, Muñoz, C, Martínez, J, Lopez, D, Ochoa, J, Andrade, J, Jaramillo, C, Garces, Gp, Botero, R, Cáceres, A, Jaramillo, M, Mejia, C, Schlesinger, A, Munevar, V, Rodriguez, J, Granados, Lm, Jaramillo, N, Aristizabal, C, Cano, N, Salazar, Jc, Urina, M, Manco, T, Valenzuela, C, Hernandez, Hj, Delgado, P, Vagner, B, Castaño, La, Ucros, P, Tellez, M, Delgado, Ja, Piedrahita, Ca, Crump, J, Fernandez, V, Quintero, Ca, Moreno, M, Hernandez Triana, E, Cuentas, I, Accini, Jl, Accini, M, Manzur, F, Rivera, E, Reynales, H, Huertas, D, Hovorka, J, Filipovsky, J, Hirmerova, J, Peska, S, Jura, R, Kanovsky, P, Herzig, R, Jansky, P, Fiala, R, Kalita, Z, Gatkova, A, Bauer, J, Fiksa, J, Sedlacek, J, Monhart, Z, Bren, J, Linhart, A, Skalicka, L, Vitovec, J, Hlinomaz, O, Parenica, J, Soucek, M, Rihacek, I, Branny, M, Sknouril, L, Klimsa, Z, Holub, M, Línkova, H, Rektor, I, Mikulik, R, Mayer O., Sr, Novakova, B, Bar, M, Brodova, P, Polasek, R, Sabl, P, Kos, P, Lorenc, Z, Macel, I, Graversen, Kh, Galatius, S, Soderberg, Lh, Sillesen, H, Madelung, S, Overgård, K, Stan, V, Rasmussen, Lh, Mortensen, B, Iversen, Hk, Back, C, Olesen, C, Christensen, H, Pedersen, A, Nielsen, T, Hasain, M, Tanggaard, L, Husted, S, Christensen, Ll, Haas, L, Mickley, H, Hosbond, S, Rosenlund, I, Jepsen, J, Kaspersen, Bb, Bronnum Schou, J, Hempel, H, Nyvad, O, Feldthaus, B, Jensen, B, Jensen, Mk, Andersen, G, Thomsen, Rb, Rokkedal, J, Joergensen, A, Bülow, M, Jeppesen, J, Lederballe, O, Scheibel, I, Sjol, A, Larsen, J, Graner, M, Svahn, T, Melin, J, Kaakkomäki, A, Airaksinen, J, Vasankari, T, Tatlisumak, T, Metso, M, Remes, A, Näppä, M, Jäkälä, P, Sivenius, J, Kalinen, M, Roine, Ro, Ketola, R, Bassand, J, Pales, D, Coisne, D, Berger, N, Galinier, M, Rosolin, N, Elbaz, M, Lacassagne, L, Montalescot, G, Vignolles, N, Gully, C, Lepage, I, Roynard, J, Hamon, M, Brucato, S, Macquin Mavier, I, Beitar, T, Berthezene, P, Medkour, T, Amarenco, P, Gueblaoui, N, Timsit, S, Riou, D, Mahagne, M, Suissa, L, Quere, I, Clouzot, S, Emmerich, J, Martinez, I, Moulin, T, Cole, M, Hosseini, H, Monod, V, Cottin, Y, Bichat, F, Galley, D, Beltra, C, Samson, Y, Pires, R, Bura Riviere, A, Pelvet, B, Giroud, M, Lecheneaut, C, Ohlmann, P, Ait m., bark Z, Farah, B, Petit, F, Caussin, C, Braun, C, Diehm, C, Mehrhof, F, Inkrot, S, Darius, H, Heinze, H, Radke, P, Kulikowsky, C, Ferrari, M, Utschig, S, Strasser, R, Haacke, K, Felix, Sb, Bruder, M, Nienaber, C, Pfaff, H, Sohn, H, Baylacher, M, Mudra, H, Setzer, P, Konstantinides, S, Hallmann, A, Kreuzer, J, Tsoy, I, Schneider, P, Appel, Kf, Habermeier, A, Zeiher, Am, Kretschmer, T, Mitrovic, V, Lehinant, S, Bohlscheid, V, Palme, B, Heuer, H, Espinola Klein, C, Savvidis, S, Kleinertz, K, Hänel, J, Schmidt, E, Schmidt, A, Ringleb, Pa, Ludwig, I, Dietzold, M, Schaffranka, A, Ranft, J, Cegla, C, Berrouschot, J, Stoll, A, Tanislav, C, Brandtner, Ma, Rosenkranz, M, Otto, D, Görtler, M, Barleben, M, Haberl, R, Miedl, S, Maschke, M, Schröder, K, Aral Becher, B, Herzog Hauff, S, Guenther, A, Herzau, C, Hoffmann, U, Roth Zetzsche, S, Grond, M, Becker, M, Hamann, G, Simon, K, Köhrmann, M, Glahn, J, Wuttig, H, Nabavi, Dg, Seraphin, D, Schellong, S, Frommhold, R, Dichgans, M, Doerr, A, Blessing, E, Buss, I, Butter, C, Bettin, D, Grosch, B, Blank, E, Wong, L, Liu, R, Lee, S, Kong, S, Yu, C, So, E, Jakal, Á, Masszi, G, Czuriga, I, Kapocsi, J, Soós, E, Csiba, L, Fekete, K, Valikovics, A, Dioszeghy, P, Muskóczki, E, Csányi, A, Matoltsy, A, Yuval, R, Bornstein, N, Elimelech, R, Chajek Shaul, T, Bursztyn, M, Hayek, T, Hazbon, K, Gavish, D, Anat, N, Wexler, D, Azar, P, Mosseri, M, Tsirulnikov, E, Rozenman, Y, Logvinenko, S, Tanne, D, Don, A, Gross, B, Feldman, Y, Klainman, E, Genin Dmitrishin, I, Eldar, M, Eizenberg, N, Atar, S, Lasri, E, Hammerman, H, Aharoni, G, Zimlichman, R, Zuker, S, Telman, G, Afanasiev, S, Katz, A, Biton, A, Goldhaber, A, Goldhaber, M, Elian, D, Linor, A, Meyuhas, S, Tsalihin, D, Kissos, D, Lampl, Y, Israelson, M, Gottlieb, S, Dotan, L, Elis, A, Karny, M, Hussein, O, Shestatski, K, Brenner, H, Segal, E, Baldini, U, Gavazzi, A, Poloni, M, Censori, B, Aiazzi, L, Maraglino, C, Marenzi, G, Specchia, G, Tritto, I, Golino, P, Cianflone, Domenico, Martignoni, A, Tamburino, C, Rubartelli, P, Ardissino, D, Tadonio, I, Stramba Badiale, M, Cernuschi, P, Nardulli, R, Sommariva, L, Giordano, A, Berni, A, Cavallini, C, Fiscella, A, Azzarelli, S, Esposito, G, Cassese, S, Danzi, G, Fattore, L, Barbieri, E, De Caterina, R, Odero, A, Puttini, M, Corrada, E, Monzini, N, Vadalà, A, Pistarini, C, Scrutinio, D, Ferratini, M, Marcheselli, S, Moretti, L, Partemi, L, Pupilella, T, Lazzari, A, Ledda, A, Geraci, G, Rasura, M, Beccia, M, Cassadonte, F, Vatrano, M, Bongiorni, D, Mos, L, Marcuzzi, G, Murena, E, Uguccioni, L, Ferretti, C, Piti ATerrosu, P, Perrone, Pf, Marconi, R, Grasso, L, Severi, S, Evola, R, Russo, N, Agnelli, G, Paci, C, Carugo, S, Silvestri, O, Testa, R, and Novo, S.

Abstract

BACKGROUND:Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1.METHODS:We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage.RESULTS:At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P

Published
2012

28. Economic consideration for reducing hospital presentations among patients with decompensated cirrhosis: not all presentations avoided can be considered equal

Author

McPhail, S.M., Horsfall, L., Irvine, K., Fagan, K.J., Powell, E.E., McPhail, S.M., Horsfall, L., Irvine, K., Fagan, K.J., and Powell, E.E.

Abstract

Individuals with decompensated cirrhosis and ascites requiring paracentesis utilize exceptionally high levels of hospital resources. Consequently, potential modifications to existing models of healthcare to assist patients in the management of their liver disease and reduce the need for hospital encounters have potential to improve patients’ health and reduce demand on acute hospital services. However, there is a paucity of data examining how much healthcare resources could be re-directed to interventions that prevent hospitalizations without net annual budgetary disadvantage (from the hospital’s perspective). The purpose of this study was to probabilistically examine how much healthcare resourcing could be saved per hospital presentation avoided among this clinical population.

Published
2015

32. Mercaptophosphonate compounds as broad-spectrum inhibitors of the metallo-beta-lactamases

Author

Lassaux, P., Hamel, M., Gulea, M., Delbrück, H., Mercuri, P.S., Horsfall, L., Dehareng, D., Kupper, M., Frere, J.-M., Hoffmann, K., Galleni, M., Bebrone, C., and Publica

Abstract

Although commercialized inhibitors of active site serine -lactamases are currently used in coadministration with antibiotic therapy, no clinically useful inhibitors of metallo--lactamases (MBLs) have yet been discovered. In this paper, we investigated the inhibitory effect of mercaptophosphonate derivatives against the three subclasses of MBLs (B1, B2, and B3). All 14 tested mercaptophosphonates, with the exception of 1a, behaved as competitive inhibitors for the three subclasses. Apart from 13 and 21, all the mercaptophosphonates tested exhibit a good inhibitory effect on the subclass B2 MBL CphA with low inhibition constants (Ki < 15 M). Interestingly, compound 18 turned out to be a potent broad spectrum MBL inhibitor. The crystallographic structures of the CphA-10a and CphA-18 complexes indicated that the sulfur atom of 10a and the phosphonato group of 18 interact with the Zn2+ ion, respectively. Molecular modeling studies of the interactions between compounds 10a and 18 and the VIM-4 (B1), CphA (B2), and FEZ-1 (B3) enzymes brought to light different binding modes depending on the enzyme and the inhibitor, consistent with the crystallographic structures.

Published
2010

34. Development and Evaluation of the Supportive Needs Assessment Tool for Cirrhosis (SNAC)

Author

Valery PC, Bernardes CM, Stuart KA, Hartel GF, McPhail SM, Skoien R, Rahman T, Clark PJ, Horsfall LU, Hayward KL, Gupta R, and Powell EE

Subjects
chronic liver disease, perceived needs, instrument validation, psychometric properties, Medicine (General), R5-920
Abstract

Patricia C Valery,1,2 Christina M Bernardes,1 Katherine A Stuart,3 Gunter F Hartel,1 Steven M McPhail,4 Richard Skoien,5 Tony Rahman,6 Paul J Clark,7 Leigh U Horsfall,2,3 Kelly L Hayward,2 Rohit Gupta,8 Elizabeth E Powell2,3 1QIMR Berghofer Medical Research Institute, Herston, QLD, Australia; 2Centre for Liver Disease Research, Translational Research Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; 3Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia; 4Centre for Functioning and Health Research, Queensland Health and the School of Public Health and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia; 5Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia; 6Gastroenterology & Hepatology Department, The Prince Charles Hospital, Chermside, QLD, Australia; 7Department of Gastroenterology and Hepatology, Mater Hospitals, Brisbane, QLD, Australia; 8Department of Gastroenterology and Hepatology, Sunshine Coast University Hospital, Birtinya, QLD, AustraliaCorrespondence: Patricia C ValeryQIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, AustraliaTel +61 7 33620376Email Patricia.Valery@qimrberghofer.edu.auBackground: We report the development and psychometric testing of a Supportive Needs Assessment tool for Cirrhosis (SNAC).Methods: The 50-item SNAC was administered to patients (n=465) diagnosed with cirrhosis recruited from five metropolitan hospitals in Queensland, Australia. Items were assessed for ceiling and floor effects, and exploratory factor analysis was used to assess the factor structure. Identified factors were assessed for internal consistency and convergent validity to validated psychosocial tools.Results: Exploratory factor analysis identified 4 factors (39 items), which together accounted for 49.2% of the total variance. The 39-item SNAC met the requirements of a needs assessment tool and identified a range of needs important to patients with cirrhosis that were grouped in four subscales: “Psychosocial issues”, “Practical and physical needs”, “Information needs”, and “Lifestyle changes”. Cronbach’s alpha values for the four subscales ranged from 0.64 to 0.92. Convergent validity was supported by a strong correlation between the total SNAC score and that of the Chronic Liver Disease Questionnaire (CLDQ; Spearman rho − 0.68; p< 0.001), and moderate correlations with the Distress Thermometer (Spearman rho 0.53; p< 0.001) and seven subscales of a generic health-related quality of life instrument (Short Form 36; Spearman rho ranged from − 0.48 to − 0.57; p< 0.001). The SNAC discriminated patient groups with respect to sex (p=0.013), age group (p< 0.001), and hospital admission status (admitted vs not; p< 0.001).Conclusion: These data provide initial evidence for the validity and reliability of the SNAC, an instrument designed to measure type and amount of perceived unmet practical and psychological needs of people diagnosed with cirrhosis.Keywords: chronic liver disease, perceived needs, instrument validation, psychometric properties

Published
2020

35. 525 BMI BUT NOT AETIOLOGY OR STAGE OF LIVER DISEASE AFFECTS THE DIAGNOSTIC SENSITIVITY OF CARBOHYDRATE DEFICIENT TRANSFERRIN

Author

Fagan, K., primary, Irvine, K., additional, McWhinney, B., additional, Fletcher, L., additional, Horsfall, L., additional, Johnson, L., additional, Clouston, A., additional, Jonsson, J., additional, O'Rourke, P., additional, Martin, J., additional, Pretorius, C., additional, Ungerer, J., additional, and Powell, E., additional

Published
2013
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39. Crystal Structure of the Mono-Zinc Metallo-beta-lactamase VIM-4 from Pseudomonas aeruginosa

Author

Lassaux, P., primary, Hamel, M., additional, Gulea, M., additional, Delbruck, H., additional, Traore, D.A.K., additional, Mercuri, P.S., additional, Horsfall, L., additional, Dehareng, D., additional, Gaumont, A.-C., additional, Frere, J.-M., additional, Ferrer, J.-L., additional, Hoffmann, K., additional, Galleni, M., additional, and Bebrone, C., additional

Published
2010
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43. Battle of Tannenberg; the action on the Russian center.

Author

Schmidt, Fedor O., Hollingsworth, George C., Horsfall, L. P., Schmidt, Fedor O., Hollingsworth, George C., Horsfall, L. P., Schmidt, Fedor O., Hollingsworth, George C., Horsfall, L. P., and Schmidt, Fedor O., Hollingsworth, George C., Horsfall, L. P.

Abstract

Includes a translation of 'Tannenberg "as it really was" by Max Hoffmann' . Chapters 12 and 13 are discussed in this study concerning the attack on the Russian forces by the Germans.

49. Childhood vitamin D deficiency in the UK : diagnosis, clinical consequences and healthcare costs

Author

Basatemur, Emre Doruk, Sutcliffe, A., Rait, G., and Horsfall, L.

Subjects
618.92
Abstract

BACKGROUND: Vitamin D has attracted considerable academic and clinical attention over the last two decades. However, the epidemiology of symptomatic vitamin D deficiency in UK children is poorly characterised, and the impact of the recent interest on paediatric clinical practice has not been explored. METHODS: A systematic review of the global incidence of symptomatic vitamin D deficiency in children was undertaken. A prospective surveillance study was conducted across the UK and Ireland to determine the incidence of hypocalcaemic seizures secondary to vitamin D deficiency in children. Cohort studies were undertaken to examine temporal trends in the diagnosis of vitamin D deficiency among children in clinical practice in the UK, and investigate healthcare expenditure related to vitamin D testing and prescribing in primary care. RESULTS: Four higher quality studies, from high-income countries with predominantly Caucasian populations, provided a pooled annual incidence estimate for symptomatic vitamin D deficiency of 3.4 per 100,000 children. The annual incidence of hypocalcaemic seizures secondary to vitamin D deficiency in the UK and Ireland was 3.5 per million children aged 0-15 years, with male infants from South Asian and black ethnic backgrounds at greatest risk. There was a 15-fold increase in the diagnosis of vitamin D deficiency among children in UK clinical practice between 2008-2014. Older age (≥10 years), non-white ethnicity, and social deprivation were associated with higher rates of diagnosis. Healthcare expenditure on vitamin D tests and prescriptions for children in primary care increased 13-fold between 2008-2014, with national costs in England estimated at £4.3 million in 2014. CONCLUSION: Considered in the context of the existing literature, these studies suggest that vitamin D deficiency may be over-tested and over-diagnosed, yet under-prevented, among children in the UK. These findings have implications for public health policy, clinical practice and health service delivery, and inform areas for future research.

Published
2018

50. A novel closed-loop biotechnology for recovery of cobalt from a lithium-ion battery active cathode material.

Author

Pakostova E, Graves J, Latvyte E, Maddalena G, and Horsfall L

Subjects
Biotechnology methods, Recycling, Bacteria metabolism, Bacteria genetics, Lithium chemistry, Electrodes, Cobalt chemistry, Electric Power Supplies
Abstract

In recent years, the demand for lithium-ion batteries (LIBs) has been increasing rapidly. Conventional recycling strategies (based on pyro- and hydrometallurgy) are damaging for the environment and more sustainable methods need to be developed. Bioleaching is a promising environmentally friendly approach that uses microorganisms to solubilize metals. However, a bioleaching-based technology has not yet been applied to recover valuable metals from waste LIBs on an industrial scale. A series of experiments was performed to improve metal recovery rates from an active cathode material (LiCoO 2 ; LCO). (i) Direct bioleaching of ≤0.5 % LCO with two prokaryotic acidophilic consortia achieved >80 % Co and 90 % Li extraction. Significantly lower metal recovery rates were obtained at 30 °C than at 45 °C. (ii) In contrast, during direct bioleaching of 3 % LCO with consortia adapted to elevated LCO levels, the 30 °C consortium performed significantly better than the 45 °C consortium, solubilizing 73 and 93 % of the Co and Li, respectively, during one-step bioleaching, and 83 and 99 % of the Co and Li, respectively, during a two-step process. (iii) The adapted 30°C consortium was used for indirect leaching in a low-waste closed-loop system (with 10 % LCO). The process involved generation of sulfuric acid in an acid-generating bioreactor (AGB), 2-3 week leaching of LCO with the biogenic acid (pH 0.9), selective precipitation of Co as hydroxide, and recirculation of the metal-free liquor back into the AGB. In total, 58.2 % Co and 100 % Li were solubilized in seven phases, and >99.9 % of the dissolved Co was recovered after each phase as a high-purity Co hydroxide. Additionally, Co nanoparticles were generated from the obtained Co-rich leachates, using Desulfovibrio alaskensis , and Co electrowinning was optimized as an alternative recovery technique, yielding high recovery rates (91.1 and 73.6% on carbon felt and roughened steel, respectively) from bioleachates that contained significantly lower Co concentrations than industrial hydrometallurgical liquors. The closed-loop system was highly dominated by the mixotrophic archaeon Ferroplasma and sulfur-oxidizing bacteria Acidithiobacillus caldus and Acidithiobacillus thiooxidans . The developed system achieved high metal recovery rates and provided high-purity solid products suitable for a battery supply chain, while minimizing waste production and the inhibitory effects of elevated concentrations of dissolved metals on the leaching prokaryotes. The system is suitable for scale-up applications and has the potential to be adapted to different battery chemistries.

Published
2024
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