Here, there and everywhere: an analysis of reference services in academic archives

The purpose of this study is to investigate how archivists conduct reference services. The investigators administered two surveys to 19 participants at 15 Canadian academic archives to understand archivists’ behaviour while performing reference. There is no standard approach to reference as many archivists use institution-specific tools coupled with their own knowledge. Finding aids are the most frequently accessed tool and are most often used in conjunction with other tools. Limited resources are the primary barrier to the provision of effective reference services. The tools that are employed by archives are archivist focused, which results in reference services that are not user focused

Toward a competency framework for Canadian archivists

The goal of this research project is to establish a foundational competency framework for Canadian archivists. This was achieved by performing a qualitative analysis of established frameworks and generating a foundational competency framework from that analysis. The framework reflects current skills and knowledge requirements. The competency framework is meant to capture all facets of managing an archives, including activities such as governance and human resources. It is intended to strike a balance among all aspects of archival practice. Future iterations should include emergent issues such as emotional labor and regional practices. This competency framework is intended to define and communicate our skills and knowledge. Its acceptance and implementation will benefit our community, our stakeholders, and our collections and will support the longevity and the prosperity of the archival profession

Development of a dual sensor polymer-based system for antibiotic detection in water samples

Ph. D. ThesisIn April 2019, the UN issued a warning that the overuse of antibiotics could lead to 10 million fatalities annually by 2050. It would also be a significant financial burden as there can be losses of €1.6 billion per single strain of antimicrobial resistant (AMR) bacteria, occurring primarily but not limited to the costs of medical care, hospitalisation, and patient care. Infiltration of antibiotics into groundwater arises from multiple sources; agriculture, highly populated residential areas and pharmaceutical effluents. These leached antibiotics journey to river systems cause selective pressure, thereby giving rise to accelerated AMR development. One route for aiding this issue is to slow the growth rate the emergence of AMR by controlling the levels of antibiotics that gain entry to water systems. To monitor this, a low-cost and reliable sensor platform is needed that can rapidly and on-site identify contaminated areas. Molecularly Imprinted Polymers (MIPs) are synthetic receptors that have potential for specific detection of contaminants in complicated matrices but have found limited commercial applications. The work within this thesis will explore the rational design of MIPs, their optimisation for a plethora of targets and the investigation of various applications to exploit their favourable characteristics when deployed as sensor platforms. Looking at how these imprinted polymers have been developed and utilised in recent times (primarily 2010-2020) and assessing any limitations encountered. These limitations have holstered MIP use, giving rise to the need for the critical review, which has been carried out in this thesis, on what development is needed to boost their applications to convert them into a mainstream commercial tool. Most MIP-based sensor systems focus primarily on a single analysis technique. Chapter 3 sees a novel, dual detection system developed which facilitates direct validation of the results and therefore can realise reliable detection of antibiotics in aqueous samples. Fluorescent monomers have been incorporated into the MIP complex allowing for fluorescent analysis as well as thermal, producing a dual sensor platform thus vastly enhancing the reliability of the biosensor. 3 Two applications of MIPs, that have been deployed as sensors, have been experimentally assessed. A focus on mounting these polymers onto Screen Printed Electrodes (SPEs) and the subsequent thermal analysis will be describe in chapter 4. This work comprised of a comparison of two techniques was carried out to determine the most appropriate method for attaching the polymers to the surface of the SPE, direct polymerisation onto the SPE against dropcasting of MIP particles synthesized by free radical polymerisation on the SPE surface. The direct polymerisation proved to afford MIP-modified SPEs to have higher levels of binding affinity. Chapter 5 explores an investigation into the evolution from small molecule targets to large macromolecules including whole bacteria. This proof-of-concept study saw a yeast mixture used as a target for MIP detection since yeast resembles bacteria in size and shape but does not need to be handled in a certified biosafety lab. A full evaluation of the work carried out concludes the thesis with an aim to gauge how the work undertaken will contribute to the development of a new division of quantitative sensor platforms. Secondly, the work produced will construct foundations for what is still needed to push the use of MIPs into commercial use to combat the rise in AMRManchester Metropolitan Universit

AKT regulates NPM dependent ARF localization and p53mut stability in tumors

Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2 activity in response to oncogenic stress, though the precise mechanism has remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers antagonizes MDM2 association with the inhibitory complex, leading to activation of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21 expression and senescence. We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status

Electrochemical and thermal detection of allergenic substance lysozyme with molecularly imprinted nanoparticles

Lysozyme (LYZ) is a small cationic protein which is widely used for medical treatment and in the food industry to act as an anti-bacterial agent; however, it can trigger allergic reactions. In this study, high-affinity molecularly imprinted nanoparticles (nanoMIPs) were synthesized for LYZ using a solid-phase approach. The produced nanoMIPs were electrografted to screen-printed electrodes (SPEs), disposable electrodes with high commercial potential, to enable electrochemical and thermal sensing. Electrochemical impedance spectroscopy (EIS) facilitated fast measurement (5–10 min) and is able to determine trace levels of LYZ (pM) and can discriminate between LYZ and structurally similar proteins (bovine serum albumin, troponin-I). In tandem, thermal analysis was conducted with the heat transfer method (HTM), which is based on monitoring the heat transfer resistance at the solid–liquid interface of the functionalized SPE. HTM as detection technique guaranteed trace-level (fM) detection of LYZ but needed longer analysis time compared to EIS measurement (30 min vs 5–10 min). Considering the versatility of the nanoMIPs which can be adapted to virtually any target of interest, these low-cost point-of-care sensors hold great potential to improve food safety

Enhanced detection of gaze toward an object: Sociocognitive influences on visual search

Funder: University of CambridgeAbstract: Another person’s gaze direction is a rich source of social information, especially eyes gazing toward prominent or relevant objects. To guide attention to these important stimuli, visual search mechanisms may incorporate sophisticated coding of eye-gaze and its spatial relationship to other objects. Alternatively, any guidance might reflect the action of simple perceptual ‘templates’ tuned to visual features of socially relevant objects, or intrinsic salience of direct-gazing eyes for human vision. Previous findings that direct gaze (toward oneself) is prioritised over averted gaze do not distinguish between these accounts. To resolve this issue, we compared search for eyes gazing toward a prominent object versus gazing away, finding more efficient search for eyes ‘gazing toward’ the object. This effect was most clearly seen in target-present trials when gaze was task-relevant. Visual search mechanisms appear to specify gazer-object relations, a computational building-block of theory of mind

Enhanced detection of gaze toward an object: Sociocognitive influences on visual search

Funder: University of CambridgeAbstract: Another person’s gaze direction is a rich source of social information, especially eyes gazing toward prominent or relevant objects. To guide attention to these important stimuli, visual search mechanisms may incorporate sophisticated coding of eye-gaze and its spatial relationship to other objects. Alternatively, any guidance might reflect the action of simple perceptual ‘templates’ tuned to visual features of socially relevant objects, or intrinsic salience of direct-gazing eyes for human vision. Previous findings that direct gaze (toward oneself) is prioritised over averted gaze do not distinguish between these accounts. To resolve this issue, we compared search for eyes gazing toward a prominent object versus gazing away, finding more efficient search for eyes ‘gazing toward’ the object. This effect was most clearly seen in target-present trials when gaze was task-relevant. Visual search mechanisms appear to specify gazer-object relations, a computational building-block of theory of mind

Systematic review of high-dose amikacin regimens for the treatment of Gram-negative infections based on EUCAST dosing recommendations

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkBackground: Updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) amikacin breakpoints for Enterobacterales and Pseudomonas aeruginosa included revised dosing recommendations of 25–30 mg/kg to achieve key pharmacokinetic/pharmacodynamic parameters, higher than recommended in the British National Formulary. The objectives of this review were to identify clinical evidence for high-dose amikacin regimens and to determine drug exposures that are related to adverse events and toxicity. Methods: The literature search was conducted in October 2021 and updated in May 2022 using electronic databases for any study reporting adult participants treated with amikacin at doses ≥20 mg/kg/day. Reference lists of included papers were also screened for potential papers. Data were extracted for pharmacokinetic parameters and clinical outcomes, presented in a summary table and consolidated narratively. Meta-analysis was not possible. Each study was assessed for bias before, during and after the intervention using the ROBINS-I tool. Results: Nine studies (total 501 participants in 10 reports) were identified and included, eight of which were observational studies. Assessment of bias showed substantial flaws. Dosing regimens ranged from 25 to 30 mg/kg/day. Six studies adjusted the dose in obesity when participants had a body mass index of ≥30 kg/m2. Target peak serum concentrations ranged from 60 mg/L to 80 mg/L and 59.6–81.8% of patients achieved these targets, but there was no information on clinical outcomes. Two studies reported the impact of high-dose amikacin on renal function. No studies reporting auditory or vestibular toxicity were identified. Conclusion: All included papers were limited by a significant risk of bias, while methodological and reporting heterogeneity made drawing conclusions challenging. Lack of information on the impact on renal function or ototoxicity means high-dose regimens should be used cautiously in older people. There is a need for a consensus guideline for high-dose amikacin to be written. Trial registration number: PROSPERO (CRD42021250022

Capacity building for conservation: problems and potential solutions for sub-Saharan Africa

To successfully achieve their stated conservation goals individuals, communities and organisations need to acquire a diversity of skills, knowledge and information (capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognised that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapidly growing number and extent of environmental problems in the region. This paper presents a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-Learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi (Kenya) in 2015. At the meeting, 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organisations from 24 African nations and 8 non-African nations. The 39 recommendations constitute five broad types of suggested action: those that recommend (i) the development of new methods, (ii) the provision of capacity building resources e.g. information or data, (iii) the communication of ideas or examples of successful initiatives, (iv) the implementation of new research or gap analyses, (v) the establishment of new structures within and between organisations, and (vi) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions. For example, all four workshops highlighted the need for a greater sense of urgency in developing capacity building activities in response to ongoing and rapid socio-environmental change in the region. Delegates also felt that conservation organisations, responsible agencies and donors need to recognise capacity building as one of the most urgent conservation issues we face. The need to develop novel and cost-efficient capacity building methodologies (and associated evaluation metrics), was also identified as a key issue. However, it was stressed that future of capacity building efforts will be best served by integrating new methods with more established activities. Importantly, given the broad suite of social, cultural and economic contexts found across sub-Saharan Africa, the need to move away from ‘one-size-fits-all’ approaches was strongly recommended in all thematic areas. Lastly, it was recognised that closing the gap between capacity need and capacity provision in the region will only be achieved through multi-partner capacity initiatives and networks.Additional co-authors: Vivian Kosgei, Anthony Kuria, Chris Magero, Maaike Manten, Paul Mugo, Eduard Müller, Julie Mulonga, Leo Niskanen, Josephine Nzilani, Mary Otieno, Nisha Owen, Juliet Owuor, Stuart Paterson, Sébastien Regnaut, Richard Rono, Joseph Ruhiu, Jesse Theuri Njoka, Lucy Waruingi, Brian Waswala Olewe and Emily Wilso