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Global consensus from the PHITT consortium surrounding an interim chemotherapy guidance for the treatment of children with hepatoblastoma, hepatocellular neoplasm – not otherwise specified (HCN-NOS), hepatocellular carcinoma and fibrolamellar carcinoma after trial closure
Get PDFMalignant liver tumors affecting children and adolescents are rare. In order to adequately study liver tumors occurring in this patient population and establish a more uniform approach to therapy, the three primary liver tumor consortia, SIOPEL (mainly European), COG (mainly North American) and JCCG (Japan), in concert, designed an international prospective clinical trial [PHITT (Paediatric Hepatic International Tumour Trial)/COGAHEP1531/JPLT4 - to be referred to as PHITT from this point forth] for the study of hepatoblastoma and hepatocellular carcinoma in children and adolescents. Recruitment to PHITT has recently concluded. The major results from this trial will be published in the next 2-3 years, therefore in the interim, we sought to provide a consensus statement on evidence-based chemotherapy guidance for hepatoblastoma and hepatocellular carcinoma of all stages
Quantum correlations in a gravitational collapse simulation with SpheriCo.jl
Get PDFWe report on work using a newly developed code, SpheriCo.jl, that computes the gravitational collapse of a spherical scalar field, where the scalar can be either a classical field, or a quantum field operator. By utilising summation-by-parts methods for the numerical derivatives we are able to simulate the collapse longer than was possible previously due to enhanced numerical stability. We present a suite of tests for the code that tests its accuracy and stability, both for the classical and quantum fields. We are able to observe critical behavior of gravitational collapse for the classical setup, in agreement with expected results. The code is also used to compute two-point correlation functions, with results that hint at a non-trivial correlation across the horizon of Hawking quanta
High-Throughput Analysis of Protein Adsorption to a Large Library of Polymers Using Liquid Extraction Surface Analysis-Tandem Mass Spectrometry (LESA-MS/MS)
Get PDFBiomaterials play an important role in medicine from contact lenses to joint replacements. High-throughput screening coupled with machine learning has identified synthetic polymers that prevent bacterial biofilm formation, prevent fungal cell attachment, control immune cell attachment and phenotype, or direct stem cell fate. In-vitro preadsorption of proteins from culture medium plays a pivotal role in controlling cell response. However, there is a paucity of studies on the screening of protein adsorption into material libraries. Here, we show how quantitative analysis of protein adsorption on a 208-member polymer microarray can be achieved using liquid extraction surface analysis, combined with an adaptation of the droplet microarray (DMA) approach and tandem mass spectrometry (LESA-MS/MS) for protein identification. This study uses a fully defined cell culture medium containing only four proteins (Essential 8) to demonstrate the feasibility of the analysis approach. Our findings show that we can generate quantitative and predictive machine learning models of protein adsorption that elucidate key polymer features that describe the relationship between surface chemistry and protein adsorption. This information is of use for the rational design of new materials with bespoke protein attachment properties for biomaterials, medical devices, or in vitro compound screening
Spaceflight redefines ageing-associated microbiota
Get PDFSpaceflight reshapes microbiota and immune function, mitigating some ageing effects while accelerating immune aging, revealing crucial insights for astronaut health and longevity in space missions
Cold War Diplomatic Surveillance: The British Government, the Chinese Mission, and the Aliens Order, August–November 1967
Get PDFThe Anglo–Chinese relationship reached a nadir during the Cultural Revolution and the Hong Kong 1967 Leftist Riots. The burning of the British Mission in Beijing and the subsequent hostage crisis further exacerbated the tensions. In response to these events, the British government–through the newly implemented Aliens Order–restricted the movement of Chinese officials in London and placed them under surveillance. The Aliens Order was a strategic move to pressure the Chinese government to address the hostage crisis and engage in diplomatic negotiations. In retaliation, the Chinese diplomatic staff in London resisted these restrictions by leveraging revolutionary diplomacy and heightening qiaowu, their overseas Chinese policy of engagement. They aimed to mobilise London’s Chinese community to counteract the British government’s actions, reflecting the broader ideological and diplomatic battles of the era. Reassessing the enactment of the Aliens Order within the context of the tumultuous events in Beijing and Hong Kong provides valuable insights into the complexities of international relations and diplomatic strategies during a period of significant global ideological conflict. This analysis delves into a specific historical conjuncture in the Anglo–Chinese relationship where the interplay between diplomacy, coercion, and community engagement in the pursuit of national interests was on full display
Mathematics provision and non-participation at advanced level in England: who is not studying post-16 mathematics?
Get PDFWhile the importance of continued mathematics study for 16–18-year-olds in England is widely agreed, recent initiatives to raise participation have muddied the waters around who is, and is not, studying post-16 mathematics. In order to find ways of extending mathematics provision to reach more students, it is necessary to determine who these non-participating students are. This paper therefore uses contemporary metaphor theory to explore the number and characteristics of non-participating students from the perspectives of three distinct metaphors: the mathematics pipeline, qualification pathways, and portfolios of mathematical competences. National participation data from the National Pupil Database are analysed for students in England that took one or more advanced level (A-level) qualifications between 2015/16 and 2020/21 (n = 796,800). The proportion of A-level students not studying any mathematics is substantially different depending on the model used, with 68% outside the mathematics pipeline and 59% not on a mathematics pathway, compared to 19% without a mathematical portfolio. In all three models, male students and those with high prior mathematics attainment were more likely to access post-16 mathematics provision. The portfolio metaphor raises further questions about what kinds of mathematics are important for all or some 16–18-year-olds to study. Access to General Mathematical Competences (GMCs) varies from 81% to 4% of A-level students, with some aspects of these competences missing from the curriculum even for students taking A-level Mathematics. Understanding these different conceptions of who is not currently studying mathematics, as well as the kinds of mathematics missing from A-level curricula, is crucial for imagining future post-16 policy and qualifications interventions
Word perception and upper-lower visual field asymmetries
No full textLeft-hemispheric lateralisation generally associates with superiority of language processing, facilitated by specialist representational and attentional influences, albeit characterised by individual differences due to handedness. In this research, we examine perceptual processing of linguistic input in left- and right-handers, and assess lateral asymmetries in the vertical dimension that is embedded within upper-lower visual fields. We use a behavioural design with presentation of bilateral stimuli (upper or lower) visual field locations during match and mismatch conditions. The data revealed that both groups were more successful in the upper than lower visual field. However, left- as compared to right-handers demonstrated increased processing in these locations, indicating beneficial effects that point to stronger perceptual responsiveness. The observations are indicative of intrinsic cross-hemispheric biases as well as acquired patterns due to perceptuo-motor experiences. In addition, hand and eye preference facilitated responses in bilateral upper visual field locations. The findings propose intricate connections between manual and attentional control with perceptual asymmetries that are steered by dedicated mechanisms. In conclusion, the data illustrate that hand and eye preference act as mediators that guide responding to visual input within the environment
Magnetic Resonance Imaging of Inner Ear and Internal Auditory Canal Structures in the Presence of a Cochlear Implant
No full textObjective To determine whether the internal auditory canal (IAC) can be visualized using magnetic resonance imaging (MRI) in users of a cochlear implant (CI) model that can safely undergo MRI at 3 T.Patients Four normally hearing controls and three individuals unilaterally implanted with a HiRes Ultra 3D (Advanced Bionics LLC, California, USA).Interventions Participants underwent 3 T MRI using sequences appropriate for the postoperative surveillance of the IAC. Images in normally hearing individuals were acquired after placing a fully functional, unpowered, CI underneath a swimming cap at each of eight candidate scalp positions, four on each side of the head. Images were compared to a control condition without a CI present. and CI users were imaged with similar sequences.Main Outcome Measures In normally hearing controls, the likely impact of the artifact on detection of pathology for multiple neuroradiological locations as rated by two independent radiologists. In CI users, a qualitative assessment of the diagnostic usability of images.Results Visibility of the ipsilateral IAC and cochlea varied among the three CI users, with images from one participant deemed largely usable, while those from the other two participants exhibited less diagnostic certainty, likely due to differences in implant locations and cranial/neuroanatomical variations. Ratings of images in normally hearing participants showed that more middle-to-anterior CI locations were associated with reduced likelihood of overlooking gross abnormalities.Conclusion Through meticulous surgical placement, bilateral IAC visualization may be achievable for monitoring chronic health conditions such as tumor surveillance in high-risk patients, and as a safety monitoring outcome measure in clinical trials
Rapid gram-scale microwave-assisted synthesis of organic anodes for sodium-ion batteries with environmental impact assessment
Get PDFDevelopment of sustainable synthesis methods of organic electrode materials (OEMs) for sodium (Na)-ion batteries must take hold rapidly in large scale-synthesis if subsequent commercialisation is to occur. We report a facile and rapid gram-scale synthesis method based on microwave irradiation for disodium naphthalene-2,6-dicarboxylate (Na-NDC) and mono/disodium benzene-1,4-dicarboxylate (Na-BDC) as model compounds. Phase purity and formation of materials was confirmed by various characterisation techniques. The electrochemical performance was tested in both half and full cell formats and compared to material obtained via smaller scale synthesis, revealing state-of-the art performance in terms of capacity retention and cyclability. The environmental impacts upon organic anode synthesis were quantified according to cradle-to-gate life cycle assessment (LCA). The results allow for the identification of environmental hotspots during production, indicating areas for future process optimisation. Interestingly, remarkably reduced impacts are obtained compared to conventional syntheses at milligram scale. Additionally, this work suggests potential significant improvements upon additional upscaling and solvent recycling
Oral hyoscine butylbromide exerts spasmolytic effects in both gastrointestinal and urogenital tissues in rats
Get PDFBackground and PurposeHyoscine butylbromide (HBB) has a low oral (PO) bioavailability. Further, limited data on its activity on non-gastrointestinal (GI) smooth muscle spasms after oral dosing are available, causing its effects beyond the GI tract to be questioned. This pharmacokinetic/pharmacodynamic (PK/PD) study, conducted using female rats, aimed to cover this gap.Experimental ApproachPK study: HBB and atropine (as a comparator agent) were administered PO and IV to rats, and concentrations in plasma and tissues (colon, uterus and urinary bladder; CUB) were measured. PD study 1: concentration–response curves of HBB and atropine (10−9–10−4 M) were obtained for carbachol-induced (10−5 M) pre-contracted tissues; PD study 2: CUB were pre-incubated with HBB and atropine at maximum concentrations (Cmax) from PK studies and carbachol concentration–response curves (10−9–10−4 M) were obtained; PD study 3: HBB and atropine were administered PO and IV to rats as for PK study, CUB tissues were collected at 0.5 h (IV) and 4 h (PO), and carbachol concentration–response curves (10−9–10−4 M) obtained.Key ResultsPO HBB showed higher Cmax in CUB tissues than in plasma. HBB and atropine reduced, concentration-dependently, carbachol-induced contractions in CUB tissues. PO HBB showed highest spasmolytic activity in colon (40%), followed by uterus (30%) and urinary bladder (10%).Conclusion and ImplicationsThis is the first comparison of PO and IV HBB and atropine in GI and non-GI tissues. Despite low bioavailability, PO HBB accumulated and exerted spasmolytic effects in tissues beyond the GI tract
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