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In Vitro and In Vivo Evaluation of Nitroxoline as an Effective Antimicrobial Alternative to Poultry Production
Get PDFBackgroundAntimicrobial resistance is a major global challenge that is exacerbated by extensive antibiotic use in livestock farming. Identifying effective alternatives to widely used human antibiotics in animal production is vital to safeguard vital human medicines and ensure sustainable food systems. Here we describe studies identifying nitroxoline (NTX) as a promising antimicrobial candidate for use in poultry production.MethodsThe antibacterial activity and resistance potential of NTX were assessed in vitro. In vivo studies in chickens evaluated tolerance, therapeutic efficacy in Salmonella-infected birds, pharmacokinetics, tissue residue depletion, growth performance, and effects on caecal microbiota. NTX was administered in-feed at different dose levels. Pharmacokinetic parameters and withdrawal periods were determined, and caecal microbiota composition was analysed using ribosomal RNA 16S sequencing.ResultsNTX exhibits potent broad-spectrum antibacterial activity in vitro and low levels of resistance. NTX is well-tolerated in chickens at 500 mg/kg in-feed for 7 days and substantially reduces liver bacterial loads at 100 mg/kg in Salmonella-infected chickens. Pharmacokinetic and residue analyses reveal NTX manifests rapid absorption and distribution, high oral bioavailability (86%), and efficient tissue clearance with a 17-day withdrawal period required for skin-plus-fat clearance. NTX supplementation is associated with increased weight gain and improved feed efficiency compared to the control group, with performance comparable to chlortetracycline. Microbiota analysis indicates modulation of caecal bacterial communities, including increased Faecalibacterium and Lactobacillus.ConclusionsThese results indicate that NTX is a viable alternative to important human antibiotics widely deployed in poultry production, offering a potential approach to minimise antimicrobial resistance whilst maintaining animal health and food biosafety
Vascularised Composite Allotransplantation: Emerging Applications in Reconstructive Surgery and Solid Organ Transplantation
Get PDFVascularised composite allotransplantation (VCA) has an evolving role in the reconstruction of complex functional and aesthetic deficits non-amenable to autologous or implant-based reconstructive modalities. International applications of VCA span upper extremity, face, abdominal wall, uterus, and penile transplantation, with more than 300 procedures performed worldwide. Among these, abdominal wall transplantation has uniquely contributed to the development of the sentinel skin flap (SSF) concept, in which solid organ transplant patients undergo simultaneous transplantation of a solid organ and a donor-derived vascularised skin flap, with the skin component of the SSF being trialled internationally as a means of monitoring for rejection within the solid organ allograft. Despite growing clinical success, VCA continues to face substantial barriers to wider adoption. Acute rejection remains highly prevalent, affecting up to 89% of recipients, with significant morbidity linked to intensive systemic immunosuppression. Challenges are further amplified by the unique immunological heterogeneity of composite grafts, ethical concerns surrounding identity-linked tissues, and the lack of standardised outcomes reporting across VCA subtypes. Advances in machine perfusion technologies and emerging cellular and biomaterial-based immunomodulation strategies show promise in reducing immunosuppression burden and improving graft longevity. This review outlines the current state of VCA, including clinical applications, outcomes, and mechanistic insights from pre-clinical studies, while highlighting key ethical considerations and evolving regulatory frameworks. Future progress will depend on standardised reporting systems, improved donor–recipient matching, better understanding of ischemia–reperfusion injury, and the development of next-generation immunosuppressive/immuno-modulatory therapies. Collectively, these innovations position VCA as a rapidly advancing field with significant potential to redefine reconstructive and transplant surgery
A multimodal Bayesian network for symptom-level depression and anxiety prediction from voice and speech data
Get PDFDuring psychiatric assessment, clinicians observe not only what patients report, but important nonverbal signs such as tone, speech rate, fluency, responsiveness, and body language. Weighing and integrating these different information sources is a challenging task and a good candidate for support by intelligence-driven tools—however this is yet to be realized in the clinic. Here, we argue that several important barriers to adoption can be addressed using Bayesian network modelling. To demonstrate this, we evaluate a model for depression and anxiety symptom prediction from voice and speech features in large-scale datasets (30,135 unique speakers). Alongside performance for conditions and symptoms (for depression, anxiety ROC-AUC = 0.842, 0.831 ECE = 0.018, 0.015; core individual symptom ROC-AUC > 0.74), we assess demographic fairness and investigate integration across and redundancy between different input modality types. Clinical usefulness metrics and acceptability to mental health service users are explored. When provided with sufficiently rich and large-scale multimodal data streams and specified to represent common mental conditions at the symptom rather than disorder level, such models are a principled approach for building robust assessment support tools: providing clinically-relevant outputs in a transparent and explainable format that is directly amenable to expert clinical supervision
Decarbonisation of the cement production process
Get PDFCement serves as the most consumed man-made material worldwide, with its production accounting for 8% of global anthropogenic carbon dioxide (CO2) emissions. Clinker, constituting 95% of cement's composition, is the primary contributor to CO2 emissions, making deep decarbonisation necessary to reduce climate change impacts. Although existing studies have tapped into fuel and calcination-oriented decarbonisation options, there is clearly a lack of a systematic comparative assessment of energy and CO2 performances focusing on alternative fuels (carbon-neutral) and alternative clinkers (characterised by low limestone content) in distinct locations, to consistently quantify their potential. This thesis addresses the literature gap through a combination of process simulation, mathematical optimisation, geospatial analysis, along with energetic and gate-to-gate CO2 performance assessments. In this thesis, fuel-based emissions were addressed through the use of hydrogen (H2) and solar energy as alternatives to fossil fuel for clinker production. This was followed by the evaluation of alternative clinkers projected to reduce CO2 emissions from limestone calcination. The findings reveal that using H2 and solar energy as alternative energy sources enables CO2 reductions of up to 27.6%. In contrast, both alternative fuel options demanded higher energy due to water electrolysis and operation of solar photovoltaics (PV) and concentrated solar power (CSP) systems. On the contrary, the use of alternative clinkers was able to achieve CO2 reductions of up to 35%, and 45.5% in energy reductions. Similarly, CO2 reductions of 45% was achieved through partial substitution of clinker with supplementary cementitious materials (SCMs) from CO2 mineralisation. Notably, the economic analysis of the solar driven process shows that in high solar regions, costs can be ~47% lower than less favourable regions, highlighting the influence of location specific solar energy characteristics. These findings accentuate the limitation of fuel substitution alone in clinker production and underscores the need for decarbonising the calcination process from the material perspective to achieve more substantial emission reductions. The collective contribution of this thesis involves insights into the carbon abatement potential from both the material and process perspectives, demonstrating the technical feasibilities of decarbonisation options
Hunger strikes among asylum seekers in Australian immigration detention: prevalence, precipitants, characteristics, and management
Get PDFBackground: Hunger strikes are commonly reported in places of detention, and Australia has some of the most restrictive immigration detention policies globally. Despite this, little is known about hunger strikes among immigration detainees in Australia. We aimed to examine the prevalence, precipitants, characteristics, and management of hunger strikes among asylum seekers in Australian onshore immigration detention. Methods: Via Freedom of Information, we obtained incident reports for all hunger strikes recorded in Australian onshore immigration detention between 3 October 2009 and 26 May 2011. Our primary methodological approach was content analysis. Data relating to hunger strike prevalence, detention type, location, gender, precipitating factors, and management of hunger strikes were extracted from each report. Hunger strike episode rates per 1000 asylum seekers were calculated using average adult population figures for 1) the entire onshore immigration detention network; 2) each held detention type (i.e., Immigration Detention Centres [IDCs], Immigration Transit Accommodation [ITA], Immigration Residential Housing [IRH], and Alternative Places of Detention [APODs]); and 3) each facility. Results: Three hundred twenty eight hunger strikes were included in the analyses. The hunger strike episode rate was 76/1000 asylum seekers (95% CI 59 – 94). On average, hunger strike episode rates were highest in IDCs (86/1000, 95% CI 68 – 104), followed by APODs (36/1000, 95% CI 24 – 48). Individual facility rates of hunger strikes ranged from 21/1000 asylum seekers (95% CI 12 – 31) in Christmas Island APODs to 317/1000 asylum seekers (95% CI 282 – 352) in Maribyrnong IDC. Compared with the average across all other facilities, hunger strike episodes were most commonly reported in Curtin IDC (126) (p < 0.001). The most reported precipitant was protest (75%). Details regarding the management of hunger strikes were noted in 7% of reports. Conclusions: Our findings highlight concerningly high rates of hunger strikes among detained asylum seekers in Australia compared to other detained populations, with protest the most common trigger. Hunger strike management was inconsistent with international best practice. These findings highlight the deleterious impact of immigration detention on the physical and mental health of those detained. Further investigation, and policy and practice development consistent with ethical and human rights frameworks are warranted
Greater visceral fat mass accumulation with high alcohol consumption
Get PDFRegular alcohol consumption is commonly perceived to contribute to abdominal adiposity, particularly visceral fat mass (VFM). Observational studies in this area have either been small or used imprecise measurement methods of VFM (e.g., waist circumference). More precise methods, such as dual-energy x-ray absorptiometry (DXA), have not been used at scale to explore the association between alcohol consumption and VFM. We investigated the relationship between alcohol consumption and VFM in a population-based cohort of n = 5 761 men and women from the Oxford Biobank who underwent a DXA-scan and provided information on regular alcohol consumption using a structured questionnaire. After adjustment for key confounders - age, smoking, height, physical activity, socio-economic status, and total fat mass (TFM) - alcohol consumption remained dose-dependently associated with VFM, in males (ß = 1.104 (1.040–1.167), p < 0.001) and females (ß = 1.102 (1.029–1.180), p = 0.006). The mean VFM percentage (%VFM) in the highest alcohol consumption quartile was over 10% greater, relative to the mean %VFM in the adjacent lower quartile, in both males (median 24 vs 12 units/week) and females (median 14 vs 7 units/week). Elevated VFM among heavier drinkers may contribute to poorer cardiovascular and metabolic health and is relevant in the search for mechanisms of regional fat repositioning
Differential self-assembly of sequence-isomeric phosphoestamers
Get PDFPhosphoestamers self-assemble into an array of superstructures according to their sequence and thus provide a useful model for understanding sequence/structure relationships. To explore this, we synthesised all tetrameric phosphoestamers composed of equal ratios of C12 and HEG monomers and examined their self-assemblies in a combined experimental/computational workflow
Measuring child development at the 2–2½-year health and development review in England: a rapid scoping review of available tools
Get PDFObjective: All children in England should receive a health review at 2–2½ years, with the Ages and Stages Questionnaire third edition (ASQ-3) used to collect public health surveillance data on child development. However, practitioners also value tools that assess individual children’s development—consistent with ASQ-3’s original purpose. Concerns about licensing costs and barriers to digitalisation have prompted interest in alternative tools to the ASQ-3 in England. Design: To inform policy, we conducted a rapid scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines to identify tools that can measure or assess early child development. Data sources: Searched PubMed, PsycINFO and Web of Science from January 2012 to November 2022, with targeted search update November 2024. Eligibility criteria: We included English-language studies published after January 2012 that described or evaluated tools in English which could measure or assess early child development in children <5 years across five domains: motor, cognitive, communicative, social and emotional. Data extraction: We extracted key features and reliability, validity, sensitivity and specificity of tools which could feasibly be implemented at the 2–2½-year review (eg, including multiple age versions and <30 min to use). We used Quality Assessment of Diagnostic Accuracy Studies-I to assess risk of bias. Results: We identified 112 unique publications describing 34 tools; six met our feasibility criteria for the 2–2½-year review (reported in 53 studies). Only ASQ-3 and CREDI offer domain-specific scoring—a government priority. ASQ-3 moderately detects mild delays and performs better for severe delays in at-risk groups. Caregiver Reported Early Development Instruments (CREDI) was designed for public health surveillance, and we do not yet know how it performs for individual assessment. Conclusions: ASQ-3 and CREDI are most promising for use at the 2–2½-year review. However, we lack UK-based validation and norming studies, even for ASQ-3. Ultimately, careful implementation and integration into existing systems will determine a tool’s value for identifying developmental needs, supporting families and producing high quality data for public health surveillance
Reperfusion grade and clinical outcome following medium vessel occlusion thrombectomy in the Endovascular Treatment to Improve Outcomes for Medium Vessel Occlusions (ESCAPE-MeVO) Trial
Get PDFBackground: Randomized trials showed that endovascular thrombectomy (EVT) did not improve outcomes in medium vessel occlusion (MeVO) stroke compared with usual care. We investigated whether patients randomized to EVT who achieved near-complete/complete reperfusion had improved clinical outcomes compared with patients randomized to usual care. Methods: Post-hoc analysis of ESCAPE-MeVO, which randomized patients with MeVO stroke to undergo EVT in addition to usual care or usual care only. Reperfusion grade in EVT patients was assessed with the MeVO expanded Thrombolysis in Cerebral Infarction (meTICI) score. Regression analyses were used to compare clinical outcomes between EVT patients with near-complete/complete (meTICI 2c-3) reperfusion and usual care patients, and the association between reperfusion grade and clinical outcomes in EVT patients. Results: Overall, 253 of 255 (99.2%) patients randomized to EVT had final meTICI scores, of whom 133 (52.2%) achieved meTICI 2c-3 reperfusion. Infarct volumes were lower in EVT meTICI 2c-3 patients than in usual care patients, but there were no significant differences between EVT meTICI 2c-3 and usual care patients for 90-day modified Rankin Scale (mRS) score (adjusted common OR 1.17, 95% CI 0.79 to 1.75). Higher final meTICI scores were associated with improved 90-day mRS and lower infarct volumes in EVT patients. Conclusion: Although higher reperfusion grade was associated with smaller infarct volumes, there was no statistically significant difference in 90-day mRS between patients achieving meTICI 2c-3 and those receiving usual care
Dynamic bacterial growth modulation in structurally distinct and functionally tuneable agarose hydrogels
Get PDFBacterial adaptability to diverse environments drives infection, persistence, and antibiotic resistance. Although hydrogels are increasingly used to model such conditions, the factors governing hydrogel-dependent bacterial growth is complex. Here, we focus on agarose hydrogels and investigate how their material properties influence bacterial proliferation. Using two agarose types – hydroxyethyl substituted and unsubstituted – at varying concentrations, we tested four bacterial species (E. coli, P. fluorescens, S. aureus, B. subtilis) across five nutrient media yielding 120 conditions. Growth consistently decreased with increasing hydrogel stiffness and water loss in unsubstituted and substituted agarose hydrogels, regardless of species. Media effects were largely due to their impact on hydrogel properties rather than nutrient content. Furthermore, electrostatic repulsion between Gram positive bacteria and anionic unsubstituted agarose suppressed growth in high concentration gels. These findings demonstrate that bacterial growth in agarose systems is primarily shaped by gel mechanics and surface interactions, informing the design of infection models and antibacterial materials