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Leveraging an epidemic to establish vaccine clinical trial capacity in a low resource setting : the Ugandan experience
Get PDFBackground Pandemics have increasingly become more frequent. Globally, between 1970 and 2016, a total of over 1770 disease outbreaks of 38 known and two unknown causes were reported. Vaccines are a key medical countermeasure for most of these outbreaks, however, most of these are developed and tested outside Sub-Saharan Africa. There is underrepresentation of Africa in vaccine clinical trials. This is attributed to poor visibility of existing sites, limited infrastructure and unpredictable regulatory timelines, and lack of capacity and infrastructure for basic science research. Main text We draw on lessons from an Ebola outbreak in Uganda to suggest key factors to establishing a vaccine trial site in a low resource setting. The factors are trained clinical trial staff, availability and adaptation of generic trial protocols, establishment of vaccine cold chain storage facilities, south-south collaborations, in-country stewardship, and close collaboration with ethical and regulatory bodies. Conclusion African institutions could capitalise on the epidemics and the accompanying responses to build capacity for vaccine trials and position themselves to take part in global vaccine trials.Peer reviewe
Click chemistry methodology : the novel paintbrush of drug design
Get PDFClick chemistry is an immensely powerful technique for the synthesis of reliable and efficient covalent linkages. When undertaken in living cells, the concept is thereby coined bioorthogonal chemistry. Used in conjunction with the photo-cross-linking methodology, it serves as a sound strategy in the exploration of biological processes and beyond. Its broad scope has led to widespread use in many disciplines; however, this Review focuses on the use of click and bioorthogonal chemistry within medicinal chemistry, specifically with regards to drug development applications, namely, the use of DNA-encoded libraries as a novel technique for lead compound discovery, as well as the synthesis of antisense oligonucleotides and protein–drug conjugates. This Review aims to provide a critical perspective and a future outlook of this methodology, such as potential widespread use in cancer therapy and personalized medicine.Peer reviewe
Gerbils without borders : invasiveness, plague, and micro-global histories of science (1932-1939)
Get PDFFunding: This work was supported by the Wellcome Trust (Grant No. ID 217988/Z/19/Z) for the project “The Global War Against the Rat and the Epistemic Emergence of Zoonosis.”In the 1930s, a series of bubonic plague outbreaks among humans cropped up in several villages at the border of Angola and Namibia. These outbreaks provoked deep concern, laying bare social and political tensions amongst neighboring imperial powers and Indigenous people within the region. Despite the appearance of this disease in what was then considered a recondite place, its spread sparked debate in transnational forums, such as the League of Nations and the Office International d’Hygiène Publique. Drawing upon archival records in Namibia, South Africa, Portugal, the United States, and the United Kingdom, this article argues that concerns over the spread of plague across land borders led to the development of a nascent invasive species framework which indicted border-crossing “migrant” South African gerbils for the international spread of the disease. It follows the transnational political and scientific dynamics created by the plague “invasion” and discusses how these, like the gerbils, crossed numerous borders and scales. Ultimately, this article shows how localized inter-species and inter-imperial encounters can provide empirical insights into the feasibilities of a micro-global history of science in which more-than-human actors take on an important role.Peer reviewe
The significance of isolated de novo red patches in the bladder in patients referred with suspected urinary tract cancer : results from the IDENTIFY study
Get PDFFunding: The authors are grateful to the Urology Foundation, Rosetrees Trust and Action Bladder Cancer UK for helping to fund the delivery of the IDENTIFY study and disseminate its results and outcomes.Objectives To assess the contemporary malignancy rate in isolated de novo red patches in the bladder and associated risk factors for better selection of red patch biopsy. Patients Patients from the IDENTIFY dataset; Patients referred to secondary care with suspected urinary tract cancer and found to have isolated de novo red patches on cystoscopy. Methods We reported the unadjusted cancer prevalence in isolated de novo red patches that were biopsied; multivariable logistic regression was used to explore cancer-associated risk factors including age, sex, smoking, type of haematuria, LUTS, UTIs and a suspicious-looking red patch (as reported by the cystoscopist). Sub-analysis of these by clinical role and experience was performed. Results A total of 1110 patients with isolated de novo red patches were included. 41.5% (n = 461) were biopsied, with a malignancy rate of 12.8% (59/461), which was significantly higher in suspicious versus non-suspicious red patches (19.1% vs. 2.81%, p < 0.01). There was a significant association between bladder cancer and age (OR 1.04, 95% CI 1.01–1.07, p = 0.01), smoking history (OR 2.62, 95% CI 1.09–6.27, p = 0.03) and suspicious-looking patch (OR 6.50, 95% CI 2.47–17.1, p < 0.01). The majority of malignancies were in over 60-year-olds. Malignancy rates in suspicious versus non-suspicious red patches did not differ significantly between clinical roles or experiences. Limitations included subjectivity in classifying a suspicious patch and selection bias as not all patches were biopsied. Conclusions Many patients still undergo unnecessary biopsies under general anaesthetic for isolated de novo red patches. Clinicians should consider the patient's age, smoking status and how suspicious-looking the patch is, before deciding on surveillance versus biopsy to improve cancer diagnostic yield.Peer reviewe
The work of the British School at Athens, 2023–2024
Get PDFThis article, based on an oral presentation in virtual format by the author at its Annual General Meeting in February 2024, summarizes the activities of the British School at Athens with a focus on the calendar year 2023. It gives us great pleasure to present the innovative and varied work of BSA sponsored field and research projects, the Fitch Laboratory, Knossos Research Centre, archive, and library as well as the inspiring work of the School students, post docs, and fellows.Peer reviewe
Impurity band formation as a route to thermoelectric power factor enhancement in n-type XNiSn half-Heuslers
Get PDFFunding: The EPSRC is acknowledged for support under award EP/N01717X/1, EP/N01703X/1, EP/X02346X/1, EP/L017008/1, EP/R023751/1 and EP/T019298/1 and for a PhD studentship for S.A.B.Bandstructure engineering is a key route for thermoelectric performance enhancement. Here, 20–50% Seebeck (S) enhancement is reported for XNiCuySn half-Heusler samples based on X = Ti. This novel electronic effect is attributed to the emergence of impurity bands of finite extent, due to the Cu dopants. Depending on the dispersion, extent, and offset with respect to the parent material, these bands are shown to enhance S to different degrees. Experimentally, this effect is controllable by the Ti content of the samples, with the addition of Zr/Hf gradually removing the enhancement. At the same time, the mobility remains largely intact, enabling power factors ≥3 mW m−1 K−2 near room temperature, increasing to ≥5 mW m−1 K−2 at high temperature. Combined with reduced thermal conductivity due to the Cu interstitials, this enables high average zT = 0.67–0.72 between 320 and 793 K for XNiCuySn compositions with ≥70% Ti. This work reveals the existence of a new route for electronic performance enhancement in n-type XNiSn materials that are normally limited by their single carrier pocket. In principle, impurity bands can be applied to other materials and provide a new direction for further development.Peer reviewe
Poly[3-methylpyridinium [(µ2-dihydrogen phosphito)bis(µ3-hydrogenphosphito)dizinc]
Get PDFIn the title compound, {C6H8N.[Zn2(HPO3)2(H2PO3)]}n, the constituent ZnO4, HPO3 and H2PO3 polyhedra of the inorganic component are linked into (010) sheets by Zn—O—P bonds (mean angle = 134.4°) and the layers are reinforced by O—H···O hydrogen bonds. The protonated templates are anchored to the inorganic sheets via bifurcated N —H···(O,O) hydrogen bonds.Peer reviewe
Investigating the time to blood culture positivity : why does it take so long?
Get PDFFunding: This work was funded by the University of St Andrews.Introduction . Bloodstream infections (BSIs) are one of the most serious infections investigated by microbiologists. However, the time to detect a BSI fails to meet the rapidity required to inform clinical decisions in real time. Gap Statement . Blood culture (BC) is considered the gold standard for diagnosing bloodstream infections. However, the time to blood culture positivity can be lengthy. Underpinning this is the reliance on bacteria replicating to a high concentration, which is necessary for the detection using routine blood culture systems. To improve the diagnosis and management of patients with BSIs, more sensitive detection methods are required. Aim . The study aimed to answer key questions addressing the delay in BSI detection and whether the time to BSI detection could be expedited using a Scattered Light Integrated Collection (SLIC) device. Methodology . A proof-of-concept study was conducted to compare the time to positivity (TTP) of Gram-negative BCs flagging positive on BacT/ALERT with an SLIC device. An SLIC device was utilized to compare the TTP of the most prevalent BSI pathogens derived from nutrient broth and BC, the influence of bacterial load on TTP and the TTP directly from whole blood. Additionally, the overall turnaround time (TAT) of SLIC was compared with that of a standard hospital workflow. Results . Most pathogens tested took significantly longer to replicate when derived from BC than from nutrient medium. The median TTP of Gram-negative BC on BacT/ALERT was 13.56 h with a median bacterial load of 6.4×109 c.f.u. ml−1. All pathogens (7/7) derived from BC at a concentration of 105 c.f.u. ml−1 were detectable in under 70 min on SLIC. Decreasing Escherichia coli BC concentration from 105 to 102 c.f.u. ml−1 increased the TTP of SLIC from 15 to 85 min. Direct BSI detection from whole blood on SLIC demonstrated a 76% reduction in TAT when compared with the standard hospital workflow. Conclusion . An SLIC device significantly reduced the TTP of common BSI pathogens. The application of this technology could have a major impact on the detection and management of BSI.Non peer reviewe
Highly conductive non-calcined 2D Cu0.3Co0.7 bimetallic–organic framework for boosting urea electrolysis in simulated seawater
Get PDFFunding: This work was supported by the University of Maragheh, Iran’s National Elites Foundation and the Iran National Science Foundation (Project Number 4037973). The authors are also grateful for the financial support.Global clean energy demands can be effectively addressed using the promising approach of hydrogen energy generation combined with less energy consumption. Hydrogen can be generated, and urea-rich wastewater pollution can be mitigated in a low-energy manner, using the urea oxidation reaction (UOR). This paper seeks to assemble a unique electrocatalyst of pristine 2D MOF, [Co(HBTC)(DMF)]n (Co-MUM-3), from 1,3,5-benzenetricarboxylate (BTC) to oxidize urea in simulated seawater. Ni foam (NF)-based working electrodes were fabricated incorporating a series of heterometallic CuCo-MUM-3 frameworks (Cu0.1Co0.9-MUM-3, Cu0.2Co0.8-MUM-3, Cu0.3Co0.7-MUM-3, and Cu0.4Co0.6-MUM-3), after which their application in urea oxidation reaction was examined. A very low required overpotential [1.26 V vs reversible hydrogen electrode (RHE) in 1M KOH + 0.5 M NaCl (simulated seawater) + 0.33M urea] and Tafel slope of 112 mV dec–1 could be observed for the Cu0.3Co0.7-MUM-3 electrocatalyst, ensuring the achievement of urea electro-oxidation and hydrogen evolution reactions at a corresponding 10 mA cm–2 electrocatalytic current density. Relatively lower overpotential will be evident compared to other reported pristine MOFs, outperforming the commercial catalyst RuO2 (1.41 V at 10 mA cm−2, 131 mV dec−1), and ensuring considerable stability at significantly high current densities for a minimum of 72 hours.Peer reviewe
Parting the waters? : dissociative identity disorder and baptism
Get PDFFunder: John Templeton Foundation.In Christian disability theology, effort has been made to better accommodate disabled persons in Christian communities and discussions of doctrine. This endeavor has encompassed discussions of both physical and psychiatric disabilities. In this paper, I will contribute to this area of research by investigating the implications of Dissociative Identity Disorder—a disorder in which a number of different personalities arise in the same body—for our understanding of baptism. I will start by providing an overview of Dissociative Identity Disorder, and will then pinpoint the question it raises regarding baptism, namely the question of whether the entire individual or particular personalities are baptized in this process. I will then propose a way of approaching this question in which our answer is dictated by the views that the personalities themselves have on their baptism. After this, I will consider an issue Dissociative Identity Disorder raises for cases of infant baptism.Peer reviewe
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