Publications by authors named "Nigel Kirby"

In gymnosperms compression wood is a specialised type of structural cell wall formed in response to biomechanical stresses. The differences in terms of gross structure, ultrastructure and chemistry are well-known. However, the differences between compression wood, normal wood, and opposite wood regarding the arrangements and interactions of the various polymers and water within their cell walls still needs to be established.

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The encapsulation of liquid crystalline phases, formed from biocompatible amphiphiles, into nanoparticles has emerged as a promising delivery strategy for hydrophilic and hydrophobic therapeutics. Strategies to characterize these delivery systems as a function of formulation parameters and aqueous environment post-manufacture are well-documented. A critical gap remains regarding the assembly kinetics and dynamics of these systems using industrially relevant manufacturing techniques.

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Hypothesis: The formation of a biomolecular corona on nanoparticle surfaces significantly influences their biological behaviour, particularly in drug delivery applications. Despite the prevalence of ingestion of particles (e.g, during oral drug delivery), our understanding of corona formation within the gastrointestinal (GI) tract remains limited, especially for non-protein components.

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Background: With greater availability of participant data and biobank repositories following clinical trial completion, adequately describing future data and biological sample reuse plans to trial participants is increasingly important. We evaluated how trial teams currently describe current and future use of participant data and biological samples in participant information leaflets (PILs).

Methods: Retrospective qualitative analysis of 240 PILs (182 clinical trials) in Ireland and the UK.

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As transient electronics continue to advance, the demand for new materials has given rise to the exploration of conducting polymer (CP)-based electronic materials. The big challenge lies in balancing conductivity while introducing controlled degradable properties into CP-based transient materials. In response to this, we present in this work a concept of using conducting polymers attached to an enzymatically biodegradable biopolymer to create transient polymer electronics materials.

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Self-assembled lipid nanoparticles (LNPs), serving as essential nanocarriers in recent COVID-19 mRNA vaccines, provide a stable and versatile platform for delivering a wide range of biological materials. Notably, LNPs with unique inverse mesostructures, such as cubosomes and hexosomes, are recognized as fusogenic nanocarriers in the drug delivery field. This study delves into the physicochemical properties, including size, lyotropic liquid crystalline mesophase, and apparent pK of LNPs with various lipid components, consisting of two ionizable lipids (ALC-0315 and SM-102) used in commercial COVID-19 mRNA vaccines and a well-known inverse mesophase structure-forming helper lipid, phytantriol (PT).

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Silicon (Si) is recognized as a promising anode material for next-generation anodes due to its high capacity. However, large volume expansion and active particle pulverization during cycling rapidly deteriorate the battery performance. The relationship between Si anode particle size and particle pulverization, and the structure evolution of Si particles during cycling is not well understood.

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Hypothesis: The self-assembly structures and phase behaviour of phospholipids in protic ionic liquids (ILs) depend on intermolecular forces that can be controlled through changes in the size, polarity, and H-bond capacity of the solvent.

Experiments: The structure and temperature stability of the self-assembled phases formed by four phospholipids in three ILs was determined by a combination of small- and wide-angle X-ray scattering (SAXS and WAXS) and small-angle neutron scattering (SANS). The phospholipids have identical phosphocholine head groups but different alkyl tail lengths and saturations (DOPC, POPC, DPPC and DSPC), while the ILs' amphiphilicity, H-bond network density and polarity are varied between propylammonium nitrate (PAN) to ethylammonium nitrate (EAN) to ethanolammonium nitrate (EtAN).

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Background: The Active Connected Engaged [ACE] study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial [RCT] with an internal pilot phase. The ACE study incorporates a multi-level mixed methods process evaluation including a systems mapping approach and an economic evaluation. ACE aims to test the effectiveness and cost-effectiveness of a peer-volunteer led active ageing intervention designed to support older adults at risk of mobility disability to become more physically and socially active within their communities and to reduce or reverse, the progression of functional limitations associated with ageing.

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Hypothesis The study aimed to use molecular hybridization of a cationic lipid with a known pharmacophore to produce a bifunctional lipid having a cationic charge to enhance fusion with the cancer cell surface and biological activity via the pharmacophoric head group. Experiments The novel cationic lipid DMP12 [N-(2-(3-(3,4-dimethoxyphenyl) propanamido) ethyl)-N-dodecyl-N-methyldodecan-1-aminium iodide] was synthesised by conjugating 3-(3,4-dimethoxyphenyl) propanoic acid (or 3,4-dimethoxyhydrocinnamic acid) to twin 12 carbon chains bearing a quaternary ammonium group [N-(2-aminoethyl)-N-dodecyl-N-methyldodecan-1-aminium iodide]. The physicochemical and biological properties of DMP12 were investigated.

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Biomimetic cubic phases can be used for protein encapsulation in a variety of applications such as biosensors and drug delivery. Cubic phases with a high concentration of cholesterol and phospholipids were obtained herein. It is shown that the cubic phase structure can be maintained with a higher concentration of biomimetic membrane additives than has been reported previously.

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Hypothesis: Dairy proteins and mono- and diglycerides (MDG) are often used in unison to tailor the properties of dairy-based emulsions. However, there are significant gaps in our understanding of how proteins affect lipid crystallisation at the oil-water interface. We have used a unique combination of interfacially-sensitive techniques to elucidate the impact of dairy proteins on interfacial MDG crystal formation.

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Through an expansive international effort that involved data collection on 12 small-angle X-ray scattering (SAXS) and four small-angle neutron scattering (SANS) instruments, 171 SAXS and 76 SANS measurements for five proteins (ribonuclease A, lysozyme, xylanase, urate oxidase and xylose isomerase) were acquired. From these data, the solvent-subtracted protein scattering profiles were shown to be reproducible, with the caveat that an additive constant adjustment was required to account for small errors in solvent subtraction. Further, the major features of the obtained consensus SAXS data over the q measurement range 0-1 Å are consistent with theoretical prediction.

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Thin, strong scaffold materials are needed for surgical applications. New materials are required, particularly those readily available, such as from non-human sources. Bovine amniotic membrane (antepartum) and equine amniotic membrane (postpartum) were characterized with tear and tensile tests.

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Background: Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs.

Methods: The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa.

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Background: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing.

Aim: To investigate the factors associated with post-consultation COPD health status in patients presenting with AECOPD in this setting.

Design And Setting: A cohort study of patients enrolled in a randomised controlled trial.

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Continuous flow injection is a key technology for serial crystallography measurements of protein crystals suspended in the lipidic cubic phase (LCP). To date, there has been little discussion in the literature regarding the impact of the injection process itself on the structure of the lipidic phase. This is despite the fact that the phase of the injection matrix is critical for the flow properties of the stream and potentially for sample stability.

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In situ small angle X-ray scattering (SAXS) measurements of ion track etching in polycarbonate foils are used to directly monitor the selective dissolution of ion tracks with high precision, including the early stages of etching. Detailed information about the track etching kinetics and size, shape, and size distribution of an ensemble of nanopores is obtained. Time resolved measurements as a function of temperature and etchant concentration show that the pore radius increases almost linearly with time for all conditions and the etching process can be described by an Arrhenius law.

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Introduction: The craniofacial abnormalities found in infants with cleft palate (CP) decrease their airway patency and increase their risk of obstructive sleep apnoea (OSA). We hypothesise that optimising sleep position in infants with CP may improve airway patency and offer a 'low-cost, high-impact' intervention to prevent the negative impacts of OSA. Because cleft centres give inconsistent advice about sleep position: some recommend back-lying and others side-lying, we will compare these in a randomised controlled trial.

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Background: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible.

Aim: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care.

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Background: The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent validity of the C3t as a simple, objective assessment of impairment that is reflective of disease severity in Huntington's, that is not reliant on clinical expertise for administration.

Methods: One-hundred-and-five participants presenting with pre-manifest (n = 16) or manifest (TFC-Stage-1 n = 39; TFC-Stage-2 n = 43; TFC-Stage-3 n = 7) Huntington's disease completed the Unified Huntington's Disease Rating Scale and the C3t at baseline.

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Huntington's disease is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington's disease is characterized by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell-replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease.

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Article Synopsis
  • The text discusses the impact of COVID-19 on pregnancy, noting associations with adverse outcomes like preterm delivery and stillbirth based on past pandemics.
  • It outlines the PAN-COVID registry, an observational study aimed at collecting data on pregnant women affected by COVID-19, which will analyze various outcomes such as miscarriage and vertical transmission of the virus to newborns.
  • The study has received ethical approval in the UK, and findings will be shared regularly with participants and collaborators via reports and online platforms to inform clinical practices and public health strategies.
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Introduction: Chronic lung disease of prematurity (CLD), also known as bronchopulmonary dysplasia (BPD), is a cause of significant respiratory morbidity in childhood and beyond. Coupled with lung immaturity, infections (especially by spp) are implicated in the pathogenesis of CLD through promotion of pulmonary inflammation. Azithromycin, which is a highly effective against spp also has potent anti-inflammatory properties.

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Background: Type I collagen is the major component of the extracellular matrix of the knee's meniscus and plays a central role in that joint's biomechanical properties. Repair and reconstruction of tissue damage often requires a scaffold to assist the body to rebuild. The middle zone of bovine meniscus is a material that may be useful for the preparation of extracellular matrix scaffolds.

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