Sodium bicarbonate ingestion and individual variability in time to peak pH

The aim of this study was to determine the individual variability in time to peak pH after the consumption of a 300mg.kg-1 dose of sodium bicarbonate (NaHCO3). Seventeen active males volunteered to participate in the study (mean ± SD: age 21.38 ± 1.5y; mass 75.8 ± 5.8kg; height 176.8 ± 7.6cm). Participants reported to the laboratory where a resting capillary blood sample was taken aseptically from the fingertip. After this, 300 mg.kg-1 of NaHCO3 in 400ml of water with 50ml of flavoured cordial was ingested. Participants then rested for 90 min during which repeated blood samples were procured at 10 minute intervals for 60 mins and then every 5 min until 90 min. Blood pH concentrations were measured using a blood gas analyser. Results suggested that time to peak pH (64.41±18.78 min) was highly variable with a range of 10-85 min and a coefficient of variation of 29.16%. A bi-modal distribution occurred, at 65 and 75 min. In conclusion, researchers and athletes, when using NaHCO3 as an ergogenic aid, should determine, in advance their time to peak pH to best utilise the added buffering capacity this substance allows

In vitro and in vivo preclinical venom inhibition assays identify metalloproteinase inhibiting drugs as potential future treatments for snakebite envenoming by Dispholidus typus

Snakebite envenoming affects more than 250,000 people annually in sub-Saharan Africa. Envenoming by Dispholidus typus (boomslang) results in venom-induced consumption coagulopathy (VICC), whereby highly abundant prothrombin-activating snake venom metalloproteinases (SVMPs) consume clotting factors and deplete fibrinogen. The only available treatment for D. typus envenoming is the monovalent SAIMR Boomslang antivenom. Treatment options are urgently required because this antivenom is often difficult to source and, at US$6000/vial, typically unaffordable for most snakebite patients. We therefore investigated the in vitro and in vivo preclinical efficacy of four SVMP inhibitors to neutralise the effects of D. typus venom; the matrix metalloproteinase inhibitors marimastat and prinomastat, and the metal chelators dimercaprol and DMPS. The venom of D. typus exhibited an SVMP-driven procoagulant phenotype in vitro. Marimastat and prinomastat demonstrated equipotent inhibition of the SVMP-mediated procoagulant activity of the venom in vitro, whereas dimercaprol and DMPS showed considerably lower potency. However, when tested in preclinical murine models of envenoming using mixed sex CD1 mice, DMPS and marimastat demonstrated partial protection against venom lethality, demonstrated by prolonged survival times of experimental animals, whereas dimercaprol and prinomastat failed to confer any protection at the doses tested. The preclinical results presented here demonstrate that DMPS and marimastat show potential as novel small molecule-based therapeutics for D. typus snakebite envenoming. These two drugs have been previously shown to be effective against Echis ocellatus VICC in preclinical models, and thus we conclude that marimastat and DMPS should be further explored as potentially valuable early intervention therapeutics to broadly treat VICC following snakebite envenoming in sub-Saharan Africa

Roadmap for a sustainable circular economy in lithium-ion and future battery technologies

The market dynamics, and their impact on a future circular economy for lithium-ion batteries (LIB), are presented in this roadmap, with safety as an integral consideration throughout the life cycle. At the point of end-of-life (EOL), there is a range of potential options—remanufacturing, reuse and recycling. Diagnostics play a significant role in evaluating the state-of-health and condition of batteries, and improvements to diagnostic techniques are evaluated. At present, manual disassembly dominates EOL disposal, however, given the volumes of future batteries that are to be anticipated, automated approaches to the dismantling of EOL battery packs will be key. The first stage in recycling after the removal of the cells is the initial cell-breaking or opening step. Approaches to this are reviewed, contrasting shredding and cell disassembly as two alternative approaches. Design for recycling is one approach that could assist in easier disassembly of cells, and new approaches to cell design that could enable the circular economy of LIBs are reviewed. After disassembly, subsequent separation of the black mass is performed before further concentration of components. There are a plethora of alternative approaches for recovering materials; this roadmap sets out the future directions for a range of approaches including pyrometallurgy, hydrometallurgy, short-loop, direct, and the biological recovery of LIB materials. Furthermore, anode, lithium, electrolyte, binder and plastics recovery are considered in order to maximise the proportion of materials recovered, minimise waste and point the way towards zero-waste recycling. The life-cycle implications of a circular economy are discussed considering the overall system of LIB recycling, and also directly investigating the different recycling methods. The legal and regulatory perspectives are also considered. Finally, with a view to the future, approaches for next-generation battery chemistries and recycling are evaluated, identifying gaps for research. This review takes the form of a series of short reviews, with each section written independently by a diverse international authorship of experts on the topic. Collectively, these reviews form a comprehensive picture of the current state of the art in LIB recycling, and how these technologies are expected to develop in the future

Metabonomic Profiling of Chicken Eggs during Storage Using High-Performance Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry

Metabonomic techniques have been used to discover subtle differences in the small-molecule profiles of chicken eggs, which could help to combat fraud within the egg industry. High-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (HPLC-Q-ToF-MS) was used to obtain profiles of the small molecules present in the yolks of chicken eggs stored for different lengths of time. Statistical analysis, including the use of XCMS Online and further exploratory statistics, was able to uncover differences in the abundances of several of the small molecules found in these egg yolks. One of these small molecules was identified through the use of METLIN and MS/MS analysis as choline. A targeted study was then carried out over a longer storage period, using the same instrumentation and analytical techniques, in order to observe how the concentration of choline in egg yolk changes over a longer period of time

Preclinical Evaluation of the Neutralising Efficacy of Three Monospecific Antivenoms Against the Venoms of Five African Echis Species, Including the Recently Partitioned E. ocellatus and E. romani

Background: The genus Echis is of high medical importance across Africa. Recently the taxonomy of its most medically important species, Echis ocellatus, underwent a revision, resulting in a splitting of the species into E. romani and E. ocellatus, and leading to uncertainty of the efficacy of antivenoms indicated for treatment of ‘E. ocellatus’ envenomings against the two redefined species.Methods: We compared the in vitro and murine preclinical venom-neutralising efficacy of three antivenoms (EchiTAbG, SAIMR Echis and Echiven) raised against E. ocellatus sensu lato against the venoms of E. romani and E. ocellatus, and investigated cross-reactivity to E. coloratus, E. leucogaster, and E. pyramidum leakeyi.Findings: In preclinical assays of envenoming, all three antivenoms neutralised Nigerian E. romani venom, though all three were less protective against Cameroonian E. romani. SAIMR Echis and Echiven neutralised E. ocellatus venom whereas EchiTAbG was less protective. SAIMR Echis and Echiven showed strong cross-reactivity to E. p. leakeyi and E. leucogaster, whilst EchiTAbG showed weaker cross-reactivity. All three antivenoms exhibited poor neutralisation of E. coloratus venom.Interpretation: This represents the first detailed analysis of differences between E. ocellatus and E. romani venom bioactivities and the impact of antivenom on these two species. Our findings demonstrate that SAIMR Echis and Echiven antivenoms are preclinically efficacious against the lethal effects of several species of Echis. These products, in addition to EchiTAbG, seem likely to meet the WHO recommendation of three antivenoms required for treatment of Echis envenomings across sub-Saharan Africa, though clinical evidence is required to confirm these findings

In vitro and in vivo preclinical venom inhibition assays identify metalloproteinase inhibiting drugs as potential future treatments for snakebite envenoming by Dispholidus typus

Snakebite envenoming affects more than 250,000 people annually in sub-Saharan Africa. Envenoming by Dispholidus typus (boomslang) results in venom-induced consumption coagulopathy (VICC), whereby highly abundant prothrombin-activating snake venom metalloproteinases (SVMPs) consume clotting factors and deplete fibrinogen. The only available treatment for D. typus envenoming is the monovalent SAIMR Boomslang antivenom. Treatment options are urgently required because this antivenom is often difficult to source and, at US$6000/vial, typically unaffordable for most snakebite patients. We therefore investigated the in vitro and in vivo preclinical efficacy of four SVMP inhibitors to neutralise the effects of D. typus venom; the matrix metalloproteinase inhibitors marimastat and prinomastat, and the metal chelators dimercaprol and DMPS. The venom of D. typus exhibited an SVMP-driven procoagulant phenotype in vitro. Marimastat and prinomastat demonstrated equipotent inhibition of the SVMP-mediated procoagulant activity of the venom in vitro, whereas dimercaprol and DMPS showed considerably lower potency. However, when tested in preclinical murine models of envenoming using mixed sex CD1 mice, DMPS and marimastat demonstrated partial protection against venom lethality, demonstrated by prolonged survival times of experimental animals, whereas dimercaprol and prinomastat failed to confer any protection at the doses tested. The preclinical results presented here demonstrate that DMPS and marimastat show potential as novel small molecule-based therapeutics for D. typus snakebite envenoming. These two drugs have been previously shown to be effective against Echis ocellatus VICC in preclinical models, and thus we conclude that marimastat and DMPS should be further explored as potentially valuable early intervention therapeutics to broadly treat VICC following snakebite envenoming in sub-Saharan Africa

Abell 1201: detection of an ultramassive black hole in a strong gravitational lens

Supermassive black holes (SMBHs) are a key catalyst of galaxy formation and evolution, leading to an observed correlation between SMBH mass MBH and host galaxy velocity dispersion σe. Outside the local Universe, measurements of MBH are usually only possible for SMBHs in an active state: limiting sample size and introducing selection biases. Gravitational lensing makes it possible to measure the mass of non-active SMBHs. We present models of the z = 0.169 galaxy-scale strong lens Abell 1201. A cD galaxy in a galaxy cluster, it has sufficient ‘external shear’ that a magnified image of a z = 0.451 background galaxy is projected just ∼1 kpc from the galaxy centre. Using multiband Hubble Space Telescope imaging and the lens modelling software PYAUTOLENS, we reconstruct the distribution of mass along this line of sight. Bayesian model comparison favours a point mass with MBH = 3.27 ± 2.12 × 1010 M⊙ (3σ confidence limit); an ultramassive black hole. One model gives a comparable Bayesian evidence without an SMBH; however, we argue this model is nonphysical given its base assumptions. This model still provides an upper limit of MBH ≤ 5.3 × 1010 M⊙, because an SMBH above this mass deforms the lensed image ∼1 kpc from Abell 1201’s centre. This builds on previous work using central images to place upper limits on MBH, but is the first to also place a lower limit and without a central image being observed. The success of this method suggests that surveys during the next decade could measure thousands more SMBH masses, and any redshift evolution of the MBH−σe relation. Results are available at https://github.com/Jammy2211/autolens_abell_1201