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Abstract Modern size exclusion chromatography (SEC) can be defined by the use of relatively small columns (e.g., 150 × 4.6 mm) packed with sub-3 μm particles, allowing a 3- to 5-fold increase in method throughput compared to that of conventional SEC. The quick success of the first sub-2 μm SEC column introduced in 2010 led to the development of numerous ultra-high performance (UHP)-SEC columns for the analysis of therapeutic monoclonal antibody (mAb)-based products. Aggregates also known as high-molecular-weight species (HMWS) are indeed one of the most important critical quality attributes (CQAs) of mAbs, as HMWS may decrease the product efficacy or cause immunogenicity effects. Therefore, the confident characterization of mAbs requires strong knowledge of not only modern SEC performance (i.e., selectivity and efficiency) but also the inherent limitations caused by non-specific interactions more likely to occur with complex antibody drug conjugates (ADCs) and some commercial mAb products. This review discusses the importance of liquid chromatographic (LC) instrumentation in order to exploit the full potential of modern SEC columns and current trends to hyphenate SEC to mass spectrometry (MS). Recent applications for antibody-based products (i.e., mAbs, ADCs, Fc-Fusion proteins and bispecific antibodies) are presented. Finally, tips and tricks are provided to further optimize SEC separations and maintaining their performance over time with better understanding of unexpected SEC results.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. For several decades, ADPKD was regarded as an adult-onset disease. In the past decade, it has become more widely appreciated that the disease course begins in childhood. However, evidence-based guidelines on how to manage and approach children diagnosed with or at risk of ADPKD are lacking. Also, scoring systems to stratify patients into risk categories have been established only for adults. Overall, there are insufficient data on the clinical course during childhood. We therefore initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for deep characterization. Methods: Global ADPedKD is an international multicenter observational study focusing on childhood-diagnosed ADPKD. This collaborative project is based on interoperable Web-based databases, comprising 7 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe, North America, South America, and the United Kingdom. In the database, a detailed basic data questionnaire, including genetics, is used in combination with data entry from follow-up visits, to provide both retrospective and prospective longitudinal data on clinical, radiologic, and laboratory findings, as well as therapeutic interventions. Discussion: The global ADPedKD initiative aims to characterize in detail the most extensive international pediatric ADPKD cohort reported to date, providing evidence for the development of unified diagnostic, follow-up, and treatment recommendations regarding modifiable disease factors. Moreover, this registry will serve as a platform for the development of clinical and/or biochemical markers predicting the risk of early and progressive disease. [Bensman, A.; Biebuyck, A.; Boyer, O.; Charbit, M.; Heidet, L.; Krid, S.; Krug, P.; Salomon, R.] Pediat Nephrol Necker Hosp, Paris, France. [Crapella, B.; Giani, M.; Mastrangelo, A.; Montini, G.] Fdn IRCCS Ca Granda, Pediat Nephrol Dialysis & Transplant Unit, Milan, Italy. [Drozdz, D.; Miklaszewska, M.; Zachwieja, K.] Jagiellonian Univ, Med Coll Cracow, Pediat Nephrol & Hypertens, Krakow, Poland. C1 [De Rechter, Stephanie; Mekahli, Djalila] Univ Hosp Leuven, Dept Pediat Nephrol, Herestr 49, B-3000 Leuven, Belgium. [De Rechter, Stephanie; Mekahli, Djalila] Katholieke Univ Leuven, Dept Dev & Regenerat, PKD Res Grp, Leuven, Belgium. [Soliman, Neveen A.] Cairo Univ, Ctr Pediat Nephrol & Transplantat, Kasr Al Ainy Sch Med, Dept Pediat, Cairo, Egypt. [Schaefer, Franz] Heidelberg Univ, Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Med Ctr, Heidelberg, Germany. [Constantinescu, I; Lungu, A. C.; Marin, A.; Negru, I; Stroescu, R.] Fundeni Clin Inst, Bucharest, Romania. [Dusan, P.; Spasojevic, B.; Stabouli, S.] Aristotle Univ Thessaloniki, Dept Pediat, Thessaloniki, Greece. [Adamczyk, P.; Bjanid, O.; Brylka, A.; Morawiec-Knysak, A.; Szczepanska, M.] Dept Pediat, Zabrze, Poland. [Bialkevich, H.; Kazyra, I] 2nd City Childrens Clin Hosp, Natl Ctr Pediat Nephrol & RRT, Minsk, BELARUS. [Liu, Isaac] Natl Univ Hlth Syst, Khoo Teck Puat Natl Univ, Childrens Med Inst, Singapore, Singapore. [Pawlak-Bratkowska, M.; Szczepanik, E.; Tkaczyk, M.] Polish Mothers Mem Hosp, Res Inst, Lodz, Poland. [Papizh, S.; Prikhodina, L.] Pirogov Russian Nat Res Med Uni, Res & Clin Inst Pediat, Moscow, Russia. [Baudouin, V; Cambier, A.; Couderc, A.; Dossier, C.; Kwon, V] Hop Robert Debre, AP HP, Paris, France. [Mallett, Andrew J.] Royal Brisbane & Womens Hosp, Conjoint Renal Res Lab, Brisbane, Qld, Australia. [Ardelean, C.; Chirita, A.; Gafencu, M.; Stroescu, R.] Timisoara Children Hosp, Timisoara, Romania. [Mallett, Andrew J.] KidGen Collaborat & Australian Genom Hlth Allianc, Melbourne, Vic, Australia. [Longo, G.; Murer, L.] Hosp Univ Padova, Pediat Nephrol Dialysis & Transplant Unit, Padua, Italy. [Godron-Dubrasquet, A.; Harambat, J.; Ilanas, B.] Bordeaux Univ Childrens Hosp, Bordeaux, France. [Karamaria, S.; Prytula, A.; Raes, A.; Snauwaert, E.; Vande Walle, J.] UZ Gent, Ghent, Belgium. [Mallett, Andrew J.] Royal Brisbane & Womens Hosp, Kidney Hlth Serv, Brisbane, Qld, Australia. [Bael, A.; Docx, M.; Segers, N.] Koningin Paola Kinderziekenhuis Antwerpen, Antwerp, Belgium. [Alpay, H.; Cicek, N.; Gokce, I] Marmara Univ, Sch Med, Div Pediat Nephrol, Istanbul, Turkey. [Schaefer, S.; Wuehl, E.] Ctr Pediat & Adolescent, Div Pediat Nephrol, Heidelberg, Germany. [Guarino, S.; La Manna, A.; Marzuillo, P.] Univ Campania Luigi Vanvitelli, Caserta, Italy. [Conceicao, M.; Teixeira, A.] Ctr Hosp Porto, Ctr Materno Infantil Norte, Porto, Portugal. [Hooman, N.; Otoukesh, H.] Iran Univ Med Sci, Aliasghar Clin Res Dev Unit, Tehran, Iran. [Guay-Woodford, Lisa M.] Childrens Natl Hlth Syst, Ctr Translat Sci, Washington, DC USA. [Caliskan, S.; Ozcan, S.; Saygili, S. K.] Istanbul Cerrahpasa Fac Med, Istanbul, Turkey. [Girisgen, I; Yuksel, S.] Pamukkale Univ, Med Fac, Dept Pediat Nephrol, Denizli, Turkey. [Aydin, Z.; Bayrakci, U. S.] Ankara Univ Hlth Sci, Child Hlth & Dis, Ankara, Turkey. [Mallett, Andrew J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Mallawaarachchi, A.; McCarthy, H.; Quinlan, C.] KidGen, Sydney, NSW, Australia. [Yildirim, Z. Y.] Istanbul Univ, Fac Med, Pediat Nephrol Dept, Istanbul, Turkey. [Dunand, O.; Leroy, V] Pediat Nephrol Unit St Denis, St Denis, Reunion, France. [Parvex, P.; Wilhelm-Bals, A.] Childrens Univ Hosp Geneva, Geneva, Switzerland. [Fila, M.; Hemery, F.; Morin, D.] CHU Arnaud Villeneuve, Montpellier, France. [Carbone, V; Diomeda, F.; Torres, D.] Pediat Nephrol Unit Bari, Bari, Italy. [Akinci, N.] Sariyer SISLI Hamidiye Etfal Res & Educ Hosp, Istanbul, Turkey. [Mallawaarachchi, A.] Royal Prince Alfred Hosp, Camperdown, NSW, Australia. [Bockenhauer, Detlef] Great Ormond St Hosp NHS Fdn Trust, London, England. [Ayasreh, N.; Furlano, M.; Torra, R.] Fundacio Puigvert, Barcelona, Spain. [Sylvestre, Lucimary C.] Hosp Pequeno Principe, Curitiba, Parana, Brazil. [Mallett, Andrew J.] Univ Queensland, Fac Med, Brisbane, Qld, Australia. [Schreuder, M.] Radboudumc Amalia Childrens Hosp, Nijmegen, Netherlands. [Espino Hernandez, M.] Hosp Infantil 12 Octubre Madrid, Madrid, Spain. [Ronit, C.] Ctr Hosp Luxembourg, Clin Pediat, Luxembourg, Luxembourg. [Eid, L. A.] Dubai Hosp, Pediat Nephrol Dept, Dubai, U Arab Emirates. [Camelio, A.; Nobili, F.; Vieux, R.] CHU Besancon, Besancon, France. [Cvetkovic, M.; Gojkovic, I] Univ Childrens Hosp, Belgrade, Serbia. [Godefroid, N.; Ranguelov, N.] Clin Univ St Luc, Brussels, Belgium. [Liebau, Max C.] Univ Hosp Cologne, Ctr Mol Med, Cologne, Germany. [Liebau, Max C.] Univ Hosp Cologne, Dept Pediat, Cologne, Germany. [Litwin, M.; Obrycki, L.] Childrens Mem Hlth Inst, Warsaw, Poland. [McCarthy, H.] Childrens Hosp Westmead, Westmead, NSW, Australia. [Mallawaarachchi, A.] Garvan Inst, Darlinghurst, NSW, Australia. [Groothoff, J. W.] Emma Childrens Hosp, Amsterdam, Netherlands. [Emma, F.; Massella, L.] Bambino Gesu Pediat Hosp, Rome, Italy. [He, G.] Foshan Women & Children Hosp, Foshan, Peoples R China. [Taranta-Janusz, K.] Dept Pediat & Nephrol, Bialystok, Poland. [McCarthy, H.] Sydney Childrens Hosp, Sydney, NSW, Australia. [Schurmans, T.; Tram, N.] CHU Charleroi, Charleroi, Belgium. [Dima, B.] Clin Europe Hop St Elisabeth, Brussels, Belgium. [Sinha, M.] Evelina London Childrens Hosp, London, England. [Helmy, R.] Cairo Univ, Kasr Al Ainy Sch Med, Cairo, Egypt. [Drube, J.; Pape, L.] Hannover Med Sch, Hannover, Germany. [Utsch, B.] Herford Hosp, Dept Paediat, Herford, Germany. [Seeman, T.] Charles Univ Prague, Prague, Czech Republic. [Thumfart, J.] Berlin Charite Univ Med, Berlin, Germany. [Gonzalez, E.] Childrens Univ Hosp, Geneva, Switzerland. [Bockenhauer, Detlef] UCL Ctr Nephrol, London, England. [Quinlan, C.] RCH Melbourne, Melbourne, Vic, Australia. [Dolan, N.] Our Ladys Childrens Hosp, Dublin, Ireland. [Seeman, T.] Motol Univ Hosp, Prague, Czech Republic. [Guffens, A.] CHC Clin Esperence, Montegnee, Belgium. [Janssens, P.] Univ Hosp Brussels, Brussels, Belgium. [Haumann, S.] Univ Klinikum Koln, Cologne, Germany. [Koenig, J.] Univ Hosp Muenster, Munster, Germany. [Ranchin, B.] Hop Femme Mere Enfant, Bron, France. [Giordano, M.] Pediat Nephrol Unit, Bari, Italy. [Collard, L.] CHR La Citadelle, Liege, Belgium. [Hansen, P.] CHU Tivoli, La Louviere, Belgium. [Lombet, J.] CHR Citadelle, Liege, Belgium. [Chiodini, B.] HUDERF, Brussels, Belgium. [Ghuysen, Ms] CHU Liege, Liege, Belgium.

Objective:Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population.Subjects:Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models.Results:We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10 ' 7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue.Conclusion:Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations. © 2018 Macmillan Publishers Limited, part of Springer Nature All rights reserved.

Abstract Aim Generalized periodic discharge (GPD) is an EEG pattern of poor neurological outcome, frequently observed in comatose patients after cardiac arrest. The aim of our study was to identify the neuronal network generating ≤2.5 Hz GPD using EEG source localization and connectivity analysis. Methods We analyzed 40 comatose adult patients with anoxic-ischemic encephalopathy, who had 19 channel-EEG recording. We computed electric source analysis based on distributed inverse solution (LAURA) and we estimated cortical activity in 82 atlas-based cortical brain regions. We applied directed connectivity analysis (Partial Directed Coherence) on these sources to estimate the main drivers. Results Source analysis suggested that the GPD are generated in the cortex of the limbic system in the majority of patients (87.5%). Connectivity analysis revealed main drivers located in thalamus and hippocampus for the large majority of patients (80%), together with important activation also in amygdala (70%). Conclusions We hypothesize that the anoxic-ischemic dysfunction, leading to hyperactivity of the thalamo-cortical (limbic presumably) circuit, can result in an oscillatory thalamic activity capable of inducing periodic cortical (limbic, mostly medial-temporal and orbitofrontal) discharges, similarly to the case of generalized rhythmic spike-wave discharge in convulsive or non-convulsive status epilepticus.

Le foie est un organe complexe qui assure des fonctions essentielles, sa défaillance entraînant un risque vital majeur. Au vu des options thérapeutiques limitées, certains dispositifs de suppléance hépatique ont été développés comme thérapie de soutien jusqu'à la transplantation du foie ou sa récupération. Ces techniques basées sur le concept de dialyse à l'albumine ont pour but l'élimination de toxines périlleuses accumulées du fait de la défaillance hépatique réfractaire. La présente thèse passe en revue les bases de ces techniques de suppléance ainsi que la littérature scientifique publiée à ce sujet. La capacité de ces techniques à remplacer partiellement la fonction de détoxication du foie a été démontrée par des études cliniques prospectives. Toutefois, la littérature à ce jour ne livre pas des conclusions définitives sur la plus-value pronostic de la suppléance hépatique artificielle. De ce fait, son utilisation ne peut être recommandée qu'en tant que thérapie de sauvetage.

The AK247 and AK248 antibodies detect the glucagon-secreting alpha cells by immunofluorescence in mice pancreatic islets.

Calderas are impressive volcanic depressions commonly produced by major eruptions. Equally impressive is the uplift of the caldera floor that may follow, dubbed caldera resurgence, resulting from magma accumulation and accompanied by minor eruptions. Why magma accumulates, driving resurgence instead of feeding large eruptions, is one of the least understood processes in volcanology. Here we use thermal and experimental models to define the conditions promoting resurgence. Thermal modelling suggests that a magma reservoir develops a growing transition zone with relatively low viscosity contrast with respect to any newly injected magma. Experiments show that this viscosity contrast provides a rheological barrier, impeding the propagation through dikes of the new injected magma, which stagnates and promotes resurgence. In explaining resurgence and its related features, we provide the theoretical background to account for the transition from magma eruption to accumulation, which is essential not only to develop resurgence, but also large magma reservoirs. Following a large caldera creating volcanic eruption, caldera resurgence may occur as magma accumulation takes place, but this rarely leads to another a major eruption. Here, the authors using thermal and experimental models show that caldera resurgence is driven by magma viscosity contrasts.