Bioequivalence studies with anti-TNF biosimilars

Introduction: Biosimilars, as defined by the European Medicines Agency, have been used in Europe since 2006. The landscape was considerably expanded when the first biosimilar of a monoclonal was approved and introduced in the European market. CT-P13 was developed by Celltrion as an infliximab biosimilar in 2013, not without controversy. As these complex molecules cannot be completely identical, some experts, clinicians, and even patients were skeptical regarding the real bioequivalence of the drugs. Currently, several new infliximab and adalimumab biosimilars are available or will reach the market in a few months. Areas covered: Our goal is to review, mainly from a clinical perspective, the available evidence for bioequivalence of anti-TNF biosimilars. We aim to take into account not only preclinical studies, mostly done for regulatory issues, but also data from clinical studies. Expert opinion: We can conclude that bioequivalence with originator is well demonstrated in those drugs which have followed European Medicines Agency regulatory pathways. Switching from originator to biosimilar appears safe for all indications. However, there are few data available for switching from one biosimilar to another, or for complete interchangeability. Prospective studies and strict pharmacovigilance are recommended

Early life risk factors and their cumulative effects as predictors of overweight in Spanish children

Objectives: To explore early life risk factors of overweight/obesity at age 6 years and their cumulative effects on overweight/obesity at ages 2, 4 and 6 years. Methods: Altogether 1031 Spanish children were evaluated at birth and during a 6-year follow-up. Early life risk factors included: parental overweight/obesity, parental origin/ethnicity, maternal smoking during pregnancy, gestational weight gain, gestational age, birth weight, caesarean section, breastfeeding practices and rapid infant weight gain collected via hospital records. Cumulative effects were assessed by adding up those early risk factors that significantly increased the risk of overweight/obesity. We conducted binary logistic regression models. Results: Rapid infant weight gain (OR 2.29, 99% CI 1.54–3.42), maternal overweight/obesity (OR 1.93, 99% CI 1.27–2.92), paternal overweight/obesity (OR 2.17, 99% CI 1.44–3.28), Latin American/Roma origin (OR 3.20, 99% CI 1.60–6.39) and smoking during pregnancy (OR 1.61, 99% CI 1.01–2.59) remained significant after adjusting for confounders. A higher number of early life risk factors accumulated was associated with overweight/obesity at age 6 years but not at age 2 and 4 years. Conclusions: Rapid infant weight gain, parental overweight/obesity, maternal smoking and origin/ethnicity predict childhood overweight/obesity and present cumulative effects. Monitoring children with rapid weight gain and supporting a healthy parental weight are important for childhood obesity prevention

The Next Generation of Axion Helioscopes: The International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) is a proposed 4th-generation axion helioscope with the primary physics research goal to search for solar axions via their Primakoff conversion into photons of 1 \u2013 10 keV energies in a strong magnetic field. IAXO will achieve a sensitivity to the axion-photon coupling ga\u3b3 down to a few 710 1212 GeV 121 for a wide range of axion masses up to 3c 0.25 eV. This is an improvement over the currently best (3rd generation) axion helioscope, the CERN Axion Solar Telescope (CAST), of about 5 orders of magnitude in signal strength, corresponding to a factor 3c 20 in the axion photon coupling. IAXO's sensitivity relies on the construction of a large superconducting 8-coil toroidal magnet of 20 m length optimized for axion research. Each of the eight 60 cm diameter magnet bores is equipped with x-ray optics focusing the signal photons into 3c 0.2 cm2 spots that are imaged by very low background x-ray detectors. The magnet will be built into a structure with elevation and azimuth drives that will allow solar tracking for 12 hours each day. This contribution is a summary of our papers [1], [2] and [3] and we refer to these for further details

The IAXO Helioscope

The IAXO (International Axion Experiment) is a fourth generation helioscope with a sensitivity, in terms of detectable signal counts, at least 104 better than CAST phase-I, resulting in sensitivity on ga¿ one order of magnitude better. To achieve this performance IAXO will count on a 8-coil toroidal magnet with 60 cm diameter bores and equipped with X-ray focusing optics into 0.20 cm2 spots coupled to ultra-low background Micromegas X-ray detectors. The magnet will be on a platform that will allow solar tracking for 12 hours per day. The next short term objectives are to prepare a Technical Design Report and to construct the first prototypes of the hardware main ingredients: demonstration coil, X-ray optics and low background detector while refining the physics case and studying the feasibility studies for Dark Matter axions

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

An update on the Axion Helioscopes front: current activities at CAST and the IAXO project

Although they have not yet been detected, axions and axion-like particles (ALPs) continue to maintain the interest (even increasingly so) of the rare-event searches community as viable candidates for the Dark Matter of the Universe but also as a solution for several other puzzles of astrophysics. Their property of coupling to photons has inspired different experimental methods for their detection, one of which is the helioscope technique. The CERN Axion Solar Telescope (CAST) is the most sensitive helioscope built up to date and has recently published part of the latest data taken with the magnet bores gradually filled with 3He, probing the mass range up to 1.17 eV. The International AXion Observatory (IAXO) is being proposed as a facility where different axion studies can be performed, with the primary goal to study axions coming from the Sun. Designed to maximize sensitivity, it will improve the levels reached by CAST by almost 5 orders of magnitude in signal detection, that is more than one order of magnitude in terms of gaγ. Here we will summarize the most important aspects of the helioscopes, and focus mainly on IAXO, based on the recent papers [1, 2]

Templated synthesis of zirconium(IV)-based metal-organic layers (MOLs) with accessible chelating sites

First published 17 Dec 2021Metal-organic layers (MOLs) are of great interest in heterogeneous catalysis, particularly materials that can accommodate extraneous metal centres. Here, we demonstrate a two-step preorganisation/delamination synthetic strategy using CuI as a template to prepare Zr-based MOLs with accessible 'syn' bis-pyrazolyl chelating sites (named UAM-2·ns) that are poised for quantitative post-synthetic metalation with late transition metals.Pol Gimeno-Fonquernie, Weibin Liang, Jorge Albalad, Andrew Kuznicki, Jason R. Price, Eric D. Bloch, Christian J. Doonan and Christopher J. Sumb

Understanding the structural landscape of Mn-based MOFs formed with hinged pyrazole carboxylate linkers

OnlinePublMetal–organic frameworks (MOFs) capable of post-synthetic metalation (PSMet) have garnered significant interest as supports for catalytic metals. The Mn-based MOF, MnMOF-1 ([Mn3(L2Me)3] where L2Me = bis- (4-carboxyphenyl-3,5-dimethylpyrazolyl)methane), has been an exemplar for studying PSMet. Herein we investigate the synthesis of Mn-based MOFs from related flexible ditopic pyrazole carboxylate links, along with the formation of MOFs with similar tetratopic hinged linkers. We show for the first time that MnMOF-1 is likely a kinetic or metastable phase and a newly identified 2D layered material (MnMOF-2D) is the thermodynamically favoured product for this metal–linker combination. Formation of a MnMOF-1 structure with shorter linkers is thwarted by steric clashes that preclude the formation of the Mn3 cluster. This observation prompted the use of density functional theory (DFT) simulations that showed the target material to be very dense, highly strained and thereby energetically unfavourable, but potentially, a hypothetical MnMOF-1 structure with a longer phenylethynyl spacer would be energetically feasible. Finally, the predominance of 2D MOFs formed with shorter flexible links encouraged us to use tetratopic hinged linkers to form 3D frameworks, which was vindicated by the successful synthesis of two new porous 3D Mn-based MOFs, MnMOF-L4 and MnMOF-L5. These results highlight that reticular synthesis of MOFs formed with flexible, non-linear linkers is challenging.Josephine F. Smernik, Pol Gimeno-Fonquernie, Jorge Albalad, Tyla S. Jones, Rosemary J. Young, Neil R. Champness, Christian J. Doonan, Jack D. Evans and Christopher J. Sumb