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In Australia, only two-thirds of doctoral students finish their degrees, with underrepresented students completing at even lower rates. Students who successfully complete still experience many challenges throughout their degrees. In this narrative literature review, we use "preparation and readiness for the doctorate" as a framework to examine how students are prepared for studies at the doctoral level, the challenges they experience, and the support that universities provide. We also weave our own stories of the doctorate to demonstrate how the issues raised in the literature play out for doctoral students. Our findings suggest that how students are prepared for the doctorate remains under-researched, with much of the literature focusing on issues that emerge once students commence, and the supports that are provided in response to these challenges. A future focus on preparation may provide insight into how institutional processes can better support doctoral students to successfully complete their degrees.

UNLABELLED: Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. IMPORTANCE: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.

UNLABELLED: Piscine lactococcosis is a significant threat to cultured and wild fish populations worldwide. The disease typically presents as a per-acute to acute hemorrhagic septicemia causing high morbidity and mortality, recalcitrant to antimicrobial treatment or management interventions. Historically, the disease was attributed to the gram-positive pathogen Lactococcus garvieae. However, recent work has revealed three distinct lactococcosis-causing bacteria (LCB)-L. garvieae, L. petauri, and L. formosensis-which are phenotypically and genetically similar, leading to widespread misidentification. An update on our understanding of lactococcosis and improved methods for identification are urgently needed. To this end, we used representative isolates from each of the three LCB species to compare currently available and recently developed molecular and phenotypic typing assays, including whole-genome sequencing (WGS), end-point and quantitative PCR (qPCR) assays, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), API 20 Strep and Biolog systems, fatty acid methyl ester analysis (FAME), and Sensititre antimicrobial profiling. Apart from WGS, sequencing of the gyrB gene was the only method capable of consistent and accurate identification to the species and strain level. A qPCR assay based on a putative glycosyltransferase gene was also able to distinguish L. petauri from L. garvieae/formosensis. Biochemical tests and MALDI-TOF MS showed some species-specific patterns in sugar and fatty acid metabolism or protein profiles but should be complemented by additional analyses. The LCB demonstrated overlap in host and geographic range, but there were relevant differences in host specificity, regional prevalence, and antimicrobial susceptibility impacting disease treatment and prevention. IMPORTANCE: Lactococcosis affects a broad range of host species, including fish from cold, temperate, and warm freshwater or marine environments, as well as several terrestrial animals, including humans. As such, lactococcosis is a disease of concern for animal and ecosystem health. The disease is endemic in European and Asian aquaculture but is rapidly encroaching on ecologically and economically important fish populations across the Americas. Piscine lactococcosis is difficult to manage, with issues of vaccine escape, ineffective antimicrobial treatment, and the development of carrier fish or biofilms leading to recurrent outbreaks. Our understanding of the disease is also widely outdated. The accepted etiologic agent of lactococcosis is Lactococcus garvieae. However, historical misidentification has masked contributions from two additional species, L. petauri and L. formosensis, which are indistinguishable from L. garvieae by common diagnostic methods. This work is the first comprehensive characterization of all three agents and provides direct recommendations for species-specific diagnosis and management.

Data process mapping is an effective way to identify data integrity vulnerabilities and remediate them. A modified example published by the Active Pharmaceutical Ingredients Committee (APIC) is reviewed critically. Can [...]

The updated version of United States Pharmacopoeia (USP) general chapter Chromatography has changes that impact chromatography parameters. In this column, we look at the current version and the update of USP on high performance liquid chromatography (HPLC) that becomes effective 1st May 2025. Do you fully understand the changes and how they will impact your laboratory?, CHROMATOGRAPHIC ANALYSIS IN regulated Good Manufacturing Practice (GMP) laboratories is under the control of pharmacopoeial general chapters. These should define the qualification parameters for instrumentation and System Suitability Test (SST) [...]

Abstract Promising therapeutic strategies are being explored to replace or regenerate the neuronal populations that are lost in patients with neurodegenerative disorders. Several research groups have attempted direct reprogramming of astrocytes into neurons by manipulating the expression of polypyrimidine tract-binding protein 1 (PTBP1) and claimed putative converted neurons to be functional, which led to improved disease outcomes in animal models of several neurodegenerative disorders. However, a few other studies reported data that contradict these claims, raising doubt about whether PTBP1 suppression truly reprograms astrocytes into neurons and the therapeutic potential of this approach. This review discusses recent advances in regenerative therapeutics including stem cell transplantations for central nervous system disorders, with a particular focus on Parkinson’s and Alzheimer’s diseases. We also provide a perspective on this controversy by considering that astrocyte heterogeneity may be the key to understanding the discrepancy in published studies, and that certain subpopulations of these glial cells may be more readily converted into neurons.

When Indigenous and non-Indigenous postgraduate research students start researching Indigenous topics, how can we best prepare them for the task ahead? In this article, I describe the approach taken by one regional Australian university to support research students with Indigenous topics through a Master of Philosophy (Indigenous). Drawing on Nakata's cultural interface theory, the programme is designed to grow students' capacities to both negotiate the intersection between Indigenous and Western knowledges and successfully complete a research thesis. This article outlines the pedagogical underpinnings of the programme and describes some of the practices used throughout one-week intensives.

The United States Food and Drug Administration (FDA) is using Remote Interactive Evaluations (RIE) to assess regulatory compliance, review submission material, or determine the timing of future inspections. Here, we look at some of the impacts of RIE on GxP laboratories. Although RIE is voluntary, is this an offer that you cannot refuse?, Since the pandemic, changes have occurred in the regulatory oversight of GxP laboratories because of travel restrictions or country access. Instead of an inspection (physical entry to a facility) via [...]

O-GlcNAcylation is an essential intracellular protein modification mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations in OGT have been linked to intellectual disability, indicating that this modification is important for the development and functioning of the nervous system. However, the processes that are most sensitive to perturbations in O-GlcNAcylation remain to be identified. Here, we uncover quantifiable phenotypes in the fruit fly Drosophila melanogaster carrying a patient-derived OGT mutation in the catalytic domain. Hypo-O-GlcNAcylation leads to defects in synaptogenesis and reduced sleep stability. Both these phenotypes can be partially rescued by genetically or chemically targeting OGA, suggesting that a balance of OGT/OGA activity is required for normal neuronal development and function.

Tired of life as your analytical results are always out of specification (OOS)? Fed up with yet another laboratory investigation? Get those rotten chromatograms to generate passing results by learning ways to manipulate peak integration from the experts... and now I have your undivided attention... and how reviewers, quality assurance (QA), and inspectors can detect them!, HOW A CHROMATOGRAPHY data system (CDS) can be involved in data falsification in regulated good practice (GXP) environments is public knowledge since the 2005 Able Laboratories fraud case (1). Chromatograms [...]

Purpose – Attention deficit hyperactivity disorder (ADHD) is a neuro-developmental condition that has frequently been pathologised in career research and broader society to date. The study seeks to reframe such assumptions through a qualitative positive-focused exploration of career stories of ADHD adults, elicited through a strength-focused technique with wide applicability for coaching and other career-based development activities. Design/methodology/approach – Situated in a strength-focused coaching psychology paradigm, the authors undertook semi-structured interviews with 17 participants, using an adapted feedforward interview technique (FFI) rooted in positive psychology (PP), to investigate individuals' strengths and successful career experiences. Findings – Narrative thematic analysis of the transcripts identified two core themes: “the paradoxical nature of strengths” and “career success as an evolving narrative”. The participants described how they have achieved career success both “in spite of” and “because of” ADHD. The use of the FFI demonstrated a helpful and easily taught method for eliciting personal narratives of success and strengths, an essential foundation to any coaching process. Originality/value – This research provides a nuanced overview, and an associated conceptual model, of how adults with ADHD perceive their career-based strengths and experiences of success. Further, the research shows the value of using a positive psychological coaching approach when working with neurominority individuals, using a successful adaptation of the FFI. The authors hope that the documentation of this technique and the resulting insights will offer important guidance for managers as coaches and internal and external career coaches, as well as providing positive and relatable narrative resources for ADHD adults.

Rare diseases affect almost 500 million people globally, predominantly impacting children and often leading to significantly impaired quality of life and high treatment costs. While significant contributions have been made to develop effective treatments for those with rare diseases, more rapid drug discovery strategies are needed. Therapeutic antisense oligonucleotides can modulate target gene expression with high specificity through various mechanisms determined by base sequences and chemical modifications; and have shown efficacy in clinical trials for a few rare neurological conditions. Therefore, this review will focus on the applications of antisense oligonucleotides, in particular splice-switching antisense oligomers as promising therapeutics for rare neurological diseases, with key examples of Duchenne muscular dystrophy and spinal muscular atrophy. Challenges and future perspectives in developing antisense therapeutics for rare conditions including target discovery, antisense chemical modifications, animal models for therapeutic validations, and clinical trial designs will also be briefly discussed.

This article explores how academic buoyancy, a concept from the educational psychology literature, can be used to understand the experiences of Indigenous secondary students’ schooling. Academic buoyancy refers to students’ ability to overcome everyday challenges of schooling. In this project, 11 Indigenous secondary students in a remote school shared their experiences of school and how they developed a range of capabilities to overcome the everyday challenges. Factors often seen as cultural impediments for Indigenous students, such as the “shame factor”, can be viewed as agentic attempts by Indigenous students to develop new capacities, such as a strategy to deal with the fear of failure. It is through these attempts that students develop strategies to negotiate the classroom without giving up their own cultural positions. This article extends earlier research on resilience to focus on the development of academically buoyant capacities that allow students to better navigate the complexities at the locale of the remote Indigenous learner.

Computerized System Validation (CSV) is usually associated with great mountains of paper (GMP). Why should this be the case? Ask yourself, am I lazy? Why write multiple documents if only one is required to validate a spectrometer with a simple intended use? Interested? Read on..., Today's the day you have been waiting for! Your brand-new UV-visible (UV-vis) or infrared (IR) spectrometer and controlling software is due to arrive in your regulated laboratory. The instrument's location [...]

A new revision to the U.S. Food and Drug Administration (FDA)'s Compliance Program Guide for Pre-Approval Inspections (PAIs) has added a fourth objective: Commitment to Quality in Pharmaceutical Development. PAIs are going to be very interesting now....., Spectroscopists usually consider chromatography as sample cleanup for their analysis. However, all spectroscopists working in regulated laboratories are living with the fallout of the 2005 fraud perpetrated by the chromatographers [...]

It is important to understand the reasons for companion animal relinquishment to help reduce the financial and ethical problems arising from too many dogs and cats in shelters. This study investigates the socioeconomic factors and reasons behind companion animal relinquishment in Australia, utilizing data from five animal shelters, over a five-year period (Financial Year 2018/19 to 2022/23). Descriptive statistics reveal that the median Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD) decile of companion animal guardians who relinquished their companion animal was decile 4 out of 10, indicating that they live in areas of lower-than-average socioeconomic status. Cats accounted for 59.4% and dogs for 40.6% of all relinquishments, with more relinquishments from lower socioeconomic deciles (1–5) (cats: 62.6%, dogs: 65.8%). The median age of relinquished cats was 5 months and dogs 16 months, with human factor-related issues (e.g., Housing, Financial Constraints, Human Healthcare) cited in 86% of cases. Descriptive analysis for the five financial years shows a declining trend in numbers of relinquishments, with housing issues (31.2%) identified as the primary reason, followed by ownership decisions (16.2%), financial constraints (11.2%), and human health issues (10.4%). Comparing the reasons for relinquishment between lower (decile 1–5) and higher (decile 6–10) socioeconomic status demonstrated that financial difficulties were a more common reason in lower vs. higher socioeconomic groups, while human health and family-related issues are more common in higher vs. lower socioeconomic groups. These findings highlight the critical role of socioeconomic factors in understanding why people relinquish their companion animals, which can inform targeted interventions to support companion animal welfare across different socioeconomic backgrounds.

The time has come for Canadians to re-envision Sir John, not by grandly reinstalling him atop a plinth but by placing him on the scales of our national history and [...]

Prehistory comprises millions of years and encompasses a diverse range of social, cultural, economic and technological practices. Despite its widespread public popularity, understanding of the chronology and developments of this vast expanse of human history is frequently anachronistic. Here, the author uses the results of museum visitor questionnaires and tracking surveys to assess public preconceptions of prehistory and engagements with museum displays. In addition, the article documents and explores 173 prehistory displays in museums in England, identifying trends in representation. The results point to some significant representational disparities affecting the display of prehistory and highlights some opportunities for reimagining museum prehistory displays. Keywords: prehistory, museums, representation, evaluation, display, visitor engagement, Introduction The temporally extensive and distant nature of prehistory reduces its relatability and accessibility for the general public. In this context, museums are highly influential in shaping how the public [...]

Computerized system validation (CSV) in good practice (GxP)-regulated laboratories is alleged to take ages and generate piles of paper to keep inspectors and auditors quiet. To the rescue is the [...]

Nick MacKinnon (Letters, November 8) offered an example of an inter-racial alien 'abduction'. More broadly, UFO hysteria has tended to be treated as a primarily US-based phenomenon. But Europe had [...]

Background: Psychomotor agitation and aggressive behaviour (AAB) have the potential to occur in any healthcare setting, including those in which Emergency Medical Services (EMS) operate. This scoping review aimed to examine the available literature on physical restraint of patients within the prehospital setting and to identify guidelines and their effectiveness, safety to patients and health care practitioners and strategies relating to physical restraint when used by EMS. Methods: We performed our scoping review using the methodological framework described by Arksey and O'Malley augmented by that of Sucharew and Macaluso. Several steps guided the review process: identification of the research question, eligibility criteria, information sources (CINAHL, Medline, Cochrane and Scopus), search, selection and data collection, ethical approval, collation, summarizing and reporting on the results. Results: The population of interest, in this scoping review was prehospital physically restrained patients, however, there was a reduced research focus on this population in comparison to the larger emergency department. Conclusion: The limitation of informed consent from incapacitated patients may relate to the lack of prospective real-world research from previous and future studies. Future research should focus on patient management, adverse events, practitioner risk, policy, and education within the prehospital setting.

Energy system models are important tools to guide our understanding of current and future carbon dioxide emissions as well as to inform strategies for emissions reduction. These models offer a vital evidence base that increasingly underpins energy and climate policies in many countries. In light of this important role in policy formation, there is growing interest in, and demands for, energy modellers to integrate more diverse perspectives on possible and preferred futures into the modelling process. The main purpose of this is to ensure that the resultant policy decisions are both fairer and better reflect people's concerns and preferences. However, while there has been a focus in the literature on efforts to bring societal dimensions into modelling tools, there remains a limited number of examples of well-structured participatory energy systems modelling processes and no available how-to guidance. This paper addresses this gap by providing good practice guidance for integrating stakeholder and public involvement in energy systems modelling based on the reflections of a diverse range of experts from this emergent field. The framework outlined in this paper offers multiple entry points for modellers to incorporate participatory elements either throughout the process or in individual stages. Recognising the messiness of both fields (energy systems modelling and participatory research), the good practice principles are not comprehensive or set in stone, but rather pose important questions to steer this process. Finally, the reflections on key issues provide a summary of the crucial challenges and important areas for future research in this critical field.

Objectives: Nutritional support is a fundamental component of holistic patient care in the intensive care unit (ICU). There is a paucity of local data pertaining to nutritional support practices at ICUs in South Africa. The aim of this study was to determine nutritional support practices at an academic hospital ICU in Johannesburg, South Africa. Methods: In this cross-sectional, descriptive and retrospective study, a simple random sampling method was utilised to select 50 data collection days from a three-month period (1 August–31 October 2018). Data relevant to the study were extracted from the ICU charts of patients who received formulae-based enteral and/or parenteral nutrition on the selected days. Charts were categorised into acute phase days (≤ 72 hours from ICU admission) and recovery phase days (> 72 hours from ICU admission). Results: A total of 387 ICU charts were included in the final sample, comprising 114 acute phase and 273 recovery phase days. Overall, enteral nutrition was prescribed on 296 (76.5%) chart days while parenteral nutrition was prescribed on 111 (28.7%) chart days. The median daily fluid balance was approximately 600 ml positive. Target protein and calorie intake was achieved on 67 (17.3%) and 110 (28.4%) chart days respectively. Conclusion: Although protein and calorie intake was suboptimal in comparison with the recommended targets, it is in keeping with general international trends. Regular audits, training of staff, attention to minimising feeding interruptions and encouraging the timely initiation of enteral nutrition are recommended interventions that may be useful in achieving nutritional targets.

The School Strike for Climate campaign led to public discussion about children's political participation. Children are generally excluded from formal political systems, however this campaign challenges mainstream attitudes that children are not sufficiently competent to participate in politics. This paper presents an analysis of Australian mainstream media representations of adult responses to the School Strike for Climate events held in Australia in March 2019. When analysed against theories of childhood, two primary narratives are reflected in what adults said about children's participation in the campaign. Anticipatory narratives focus on children appropriately developing into adults, and are represented by the notion that strikers should be in school, be punished for missing school, and are 'just kids' who should not be listened to. Protectionist narratives seek to shelter children from adult matters, suggesting strikers were brainwashed and raising welfare concerns. Neither of these narratives regard children as citizens capable of political voice, despite these children acting prefiguratively to create a world in which their civic participation is valued. Social movement theories of prefiguration are also explored in this paper, providing a counter argument to suggestions that children have no political agency and should be excluded from activism and discussions regarding climate change.