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To determine the effect of distributed practice (spacing out of study over time) and retrieval practice (recalling information from memory) on academic grades in health professions education and to summarise a range of interventional variables that may affect study outcomes. A systematic search of seven databases in November 2022 which were screened according to predefined inclusion criteria. The Medical Education Research Study Quality Instrument (MERSQI) and Newcastle-Ottawa Scale-Education (NOS-E) were used to critically appraise eligible articles. A summary of interventional variables includes article content type, strategy type, assessment type and delay and statistical significance. Of 1818 records retrieved, 56 were eligible for inclusion and included a total of 63 experiments. Of these studies, 43 demonstrated significant benefits of distributed practice and/or retrieval practice over control and comparison groups. Included studies averaged 12.23 out of 18 on the MERSQI and averaged 4.55 out of 6 on the NOS-E. Study designs were heterogeneous with a variety of interventions, comparison groups and assessment types. Distributed practice and retrieval practice are effective at improving academic grades in health professions education. Future study quality can be improved by validating the assessment instruments, to demonstrate the reliability of outcome measures. Increasing the number of institutions included in future studies may improve the diversity of represented study participants and may enhance study quality. Future studies should consider measuring and reporting time on task which may clarify the effectiveness of distributed practice and retrieval practice. The stakes of the assessments, which may affect student motivation and therefore outcomes, should also be considered.

Universities globally have been increasingly looking to bring in professionals with expertise in learning and curriculum design to help with educational innovation. The aim of this study was to explore the epistemological views of learning that people in curriculum and learning design roles use to inform their practice. In this study, ten learning and curriculum designers were interviewed in depth. The participants demonstrated wide and deep knowledge of learning and teaching, drawing on both established notions of constructivism but also on emerging theories and evidence. Combined with extensive experience, the interviews revealed that these learning designers demonstrate high levels of epistemic fluency, adapting and using processes and practices in a dynamic way as task requirements demand. The findings make a contribution to the limited understanding of the knowledge base that curriculum learning designers draw on to carry out their work. The implications of these findings for universities are also discussed.

Surviving and thriving in this 21st century volatile, uncertain, complex, and ambiguous (VUCA) world caused by rapid digitalisation and changing work landscape, requires agile organisations with agile employees who are adaptable, resilient, and actively engaged in lifelong learning. A blended workforce encompassing full-time and 'gig' employees, working in tandem with smart machines, calls for an innovative and collaborative workforce capable of critical thinking and creative problem solving. This paper aims to highlight the potential of design thinking approaches to foster lifelong learning and graduate employability in a VUCA environment. The paper outlines an empirical study investigating the multiple benefits of incorporating design thinking process attributes in higher education. It argues that such processes can result in the development of 21st century skills and mindset and graduate capability themes that promote lifelong learning skills. Incorporating such strategies offers the potential to narrow the competency gap between workforce and work and enhance the employability and career development of graduates. The paper offers a Framework for Lifelong Learning in a VUCA environment that outlines the powerful traits that arise as payoffs from engaging in and practising design thinking. This framework can serve as a preliminary guide for higher education educators, learning organisations and individuals to inculcate and enhance lifelong learning.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

Loeffler first described “fibroplastic parietal endocarditis with blood eosinophilia” in 1936. This we now know refers to the most common cardiac manifestation of an uncommon condition, the so-called hypereosinophilic syndromes. This condition typically results in a restrictive cardiomyopathy affecting the left heart, but here, we present an unusual case of a 65-year-old woman with chronic hypereosinophilia of at least 2 years, who presented with right heart failure as a result of eosinophilic endomyocardial infiltration of her right ventricle. We explore the diagnostic pathway and look at the literature on management.

Contributions: This article provides valuable insights into the varying approaches of engineering students in their understanding and application of project-based learning (PBL) and its relationship with student success. The findings can be used to improve the design and implementation of effective learning environments, evaluate the effectiveness of engineering education programs, and advance the current understanding of the relationship between PBL and knowledge acquisition in engineering. Background: Previous research has demonstrated that PBL has become a significant teaching and learning method in engineering education. It has resulted in considerable progress in students' problem-solving and critical thinking skills, teamwork, and technical concept communication. However, there is still a lack of exploration on how engineering students perceive PBL from their standpoint and how their conceptions influence student learning. This study aims to contribute to the currently limited comprehension of PBL from the students' perspective. Research Questions: What are the qualitatively different ways engineering students conceptualize PBL, and how does PBL contribute to knowledge and skill acquisition? Methodology: A phenomenographic approach was used to gather data from engineering students who had experienced PBL in their course. Semi-structured interviews were conducted to gather rich and detailed data about the students' conceptions of PBL. The data was then analyzed using a phenomenographic framework to identify how engineering students conceived PBL. Findings: Students' conceptions of PBL are not uniform but vary in five different pedagogical beliefs that shape how they act in the PBL environment. The different conceptions of PBL in engineering education suggest that instructors need to communicate the learning objectives of PBL more clearly to students, and design PBL activities that cater to the diverse needs and expectations of students.

This paper reports on a research project that heard the perspectives on and experiences of the Relationships and Sexuality Education (RSE) programme of a range of stakeholders in post-primary schools. The researchers listened to students aged from 13 to 18 years, to teachers of RSE, to principals and to parents/guardians in six post-primary schools across the Republic of Ireland. We found that teacher comfortability is one of the key components in the delivery of high-quality and effective RSE. By 'comfortability' we mean knowledge, expertise, confidence and appropriate pedagogical skills to teach this particular material. This view was shared by students, teachers, principals as well as some parents who commented on this aspect of RSE. We found that there are several factors that impede teacher comfortability, namely lack of qualification in Social Personal and Health Education/RSE, lack of initial teacher education input in this area, limited access to continuing professional development, an absence of mandated curriculum content and fear of external criticism especially by parents. Our findings are very similar to those of the NCCA [2019. Report on the Review of Relationships and Sexuality Education (RSE) in Primary and Post-Primary Schools. December. Dublin: NCCA] evaluation that took place in a similar time-frame and included a similar range of participants.

Abstract By presenting the most up‐to‐date findings and incorporating the latest evidence, this article seeks to present a comprehensive guide for navigating the complexities inherent in the management of colorectal liver metastasis. It aims to serve as a valuable resource offering clinicians and healthcare professionals an understanding of the diverse modalities and approaches available for treating this challenging and multifaceted disease. In an era of rapidly evolving medical knowledge, this article examines the latest insights to make informed decisions in the realm of colorectal liver metastasis management. The article does not only highlight the up‐to‐date knowledge but also provides the evidence for existing therapeutic strategies. This practical tool provides evidence‐based recommendations to clinicians, thereby contributing to the ongoing advancement of effective treatment strategies for this challenging disease.

The last decade has witnessed significant progress towards zero-emission electric aviation. Lithium-ion batteries are at the centre of this technological transformation. However, electric flight requires suitable considerations for safety concerns associated with Lithium-ion batteries. Fault diagnostic approaches aimed at validating the safety of batteries before every flight have emerged as an attractive prospect. In this pursuit, a three-paper series proposing a novel fault diagnosis algorithm is presented. The algorithm is capable of diagnosing faults in an aircraft battery using the data collected during charging and was previously validated for a particular cell type under steady charging conditions. In this paper, two extensional aspects of the algorithm are investigated: cell-to-cell transferability and disparate charging conditions. While crucial for practical implementation, these aspects were overlooked in previous literature. Through experiments conducted at module-level, it was revealed that the algorithm could diagnose faults for a different cell type with minimal preliminary cell-level characterisation, thus demonstrating its ease of transferability. Moreover, modifications introduced in the algorithm enabled it to perform fault diagnosis under unsteady charging conditions for an aerospace module despite significant internal temperature gradients. Thus, the successful working of the algorithm in the considered aspects, which are unprecedented in literature, prove its feasibility for real-life application.

The rapid advancement of technology, alongside state-of-the-art techniques is at an all-time high. However, this unprecedented growth of technological prowess also brings forth potential threats, as oftentimes the security encompassing these technologies is imperfect. Particularly within the automobile industry, the recent strides in technology have brought about increased complexity. A notable flaw lies in the CAN-FD protocol, which lacks robust security measures, making it vulnerable to data theft, injection, replay, and flood data attacks. With the rising complexity of in-vehicular networks and the widespread adoption of CAN-FD, the imperative to safeguard the protocol has never been more crucial. This paper aims to provide a comprehensive review of the existing in-vehicle communication protocol, CAN-FD. It explores existing security approaches designed to fortify CAN-FD, demonstrating multiple multi-layer solutions that leverage modern techniques including Physical Unclonable Function (PUF), Elliptical Curve Cryptography (ECC), Ethereum Blockchain, and Smart contracts. The paper highlights existing multi-layer security measures that offer minimal overhead, optimal performance, and robust security. Moreover, it identifies areas where these security measures fall short and discusses ongoing research along with suggestions for implementing software and hardware-level modifications. These proposed changes aim to streamline complexity, reduce overhead while ensuring forward compatibility. In essence, the methods outlined in this study are poised to excel in real-world applications, offering robust protection for the evolving landscape of in-vehicular communication systems.

Abstract The majority of research into the mental health benefits of blue space (outdoor places where water is a central feature) has focussed on the associations between neighbourhood exposure to these spaces and population‐level incidence of unipolar depression or anxiety disorder. There has been little exploration of the therapeutic use of blue space by those navigating bipolar, schizophrenia or other psychotic conditions. Knowledge arising from such an exploration could assist in the design and optimisation of nature‐based care for people with these conditions, as well as with self‐management. We conducted semi‐structured online and telephone interviews with 19 adults who self‐reported experience of these conditions. Interviews were conducted in the United Kingdom from August to December 2021. We describe four of the key interpretive themes identified via an in‐depth inductive thematic analysis of the interview transcripts to highlight how participants sought out moments of affective sanctuary through their blue encounters. Blue spaces were described as having the potential to reset the mind, emotions and body. This was in part due to their socially undemanding nature, and ability to provide respite from a socially stressful world. Participants described developing a blue identity, whereby a sense of attachment to and shared history with these places was articulated as well as incorporating blue spaces into self‐ and emotion‐regulation practices. Finally, participants described experiences of and recommendations for a therapeutic blue intervention. The role of biodiversity in contributing to the benefits of blue spaces was implied primarily in terms of perceived soundscapes, but also through visual observations. Synthesis and applications. Blue care for people with bipolar, schizophrenia or other psychotic conditions should consider the need that some individuals have for solitude and proximity to their home when they visit blue spaces, as well as individual differences in the features of blue space interactions that provide the greatest benefit. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background The international scale and spread of evidence-based perioperative medicine for older people undergoing surgery (POPS) services has not yet been fully realised. Implementation science provides a structured approach to understanding factors that act as barriers and facilitators to the implementation of POPS services. In this study, we aimed to identify factors that influence the implementation of POPS services in the UK. Methods A qualitative case study at three UK health services was undertaken. The health services differed across contextual factors (population, workforce, size) and stages of POPS service implementation maturity. Semi-structured interviews with purposively sampled clinicians (perioperative medical, nursing, allied health, and pharmacy) and managers (n = 56) were conducted. Data were inductively coded, then thematically analysed using the Consolidated Framework for Implementation Research (CFIR). Results Fourteen factors across all five CFIR domains were relevant to the implementation of POPS services. Key shared facilitators included stakeholders understanding the rationale of the POPS service, with support from their networks, POPS champions, and POPS clinical leads. We found substantial variation and flexibility in the way that health services responded to these shared facilitators and this was relevant to the implementation of POPS services. Conclusions Health services planning to implement a POPS service should use health service-specific strategies to respond flexibly to local factors that are acting as barriers or facilitators to implementation. To support implementation of a POPS service, we recommend health services prioritise understanding local networks, identifying POPS champions, and ensuring that stakeholders understand the rationale for the POPS service. Our study also provides a structure for future research to understand the factors associated with ‘unsuccessful’ implementation of a POPS service, which can inform ongoing efforts to implement evidence-based perioperative models of care for older people.

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p

The Self-Regulation for Learning Online (SRL-O) questionnaire was developed to encompass the breadth of motivational beliefs and learning strategies that are often used in online and/or blended learning contexts. No current measure meets all these needs. This study used two non-duplicate samples to provide evidence of the psychometric properties of SRL-O using exploratory factor analyses (sample 1, n = 313), and confirmatory factor analyses, convergent and content validity and reliability (sample 2, n = 321). The SRL-O has a 10-factor structure, made up of (1) online self-efficacy, (2) online intrinsic motivation, (3) online extrinsic motivation, (4) online negative achievement emotion, (5) planning and time management, (6) metacognition, (7) study environment, (8) online effort regulation, (9) online social support, and (10) online task strategies. The SRL-O was also found to have two superordinate factors (motivational beliefs and learning strategies). The SRL-O was demonstrated to be a psychometrically sound measure of online SRL for learners studying in online and blended learning contexts. There is no other online self-regulated learning questionnaire that currently covers such a wide range of motivational beliefs and learning strategies.

One of the ways in which students can be taught science is by doing science, the intention being to help students understand the nature, processes, and methods of science. Investigative research projects may be used in an attempt to reflect some aspects of science more authentically than other teaching and learning approaches, such as confirmatory practical activities and teacher demonstrations. In this article, we are interested in the affordances of investigative research projects where students, either individually or collaboratively, undertake original research. We provide a critical rather than a systematic review of the field. We begin by examining the literature on the aims of science education, and how science is taught in schools, before specifically turning to investigative research projects. We examine how such projects are typically undertaken before reviewing their aims and, in more detail, the consequences for students of undertaking such projects. We conclude that we need social science research studies that make explicit the possible benefits of investigative research projects in science. Such studies should have adequate control groups that look at the long-term consequences of such projects not only by collecting delayed data from participants, but by following them longitudinally to see whether such projects make any difference to participants' subsequent education and career destinations. We also conclude that there is too often a tendency for investigative research projects for students in science to ignore the reasons why scientists work in particular areas and to assume that once a written report of the research has been authored, the work is done. We therefore, while being positive about the potential for investigative research projects, make specific recommendations as to how greater authenticity might result from students undertaking such projects.

Objective To gather a deep qualitative understanding of the perceived benefits and impacts of External-Beam RadioTherapy (EBRT) and TARGeted Intraoperative radioTherapy (TARGIT-IORT) using Intrabeam to assess how the treatments affected patient/care partner experiences during their cancer treatment and beyond.Design and participants A patient-led working group was established to guide study design and to help validate findings. Patients with experience of receiving EBRT or TARGIT-IORT were purposively sampled by Hampshire Hospitals NHS Foundation Trust. These patients had been offered both regimens as per their clinical features and eligibility. Semistructured interviews were conducted with 29 patients and care partners with lived experience of either EBRT (n=12, 5-day FAST-Forward regimen and n=3, 3-week regimen) or TARGIT-IORT (n=14). Thematic analysis was then carried out by two coders generating 11 themes related to EBRT or TARGIT-IORT.Setting Semistructured interviews were conducted virtually via Zoom during February and March 2023.Results A number of procedural grievances were noted among EBRT patients. EBRT was perceived as being disruptive to normal routines (work, home and travel) and caused discomfort from side effects. TARGIT-IORT was perceived by patients and care partners as the safer option and efficient with minimal if any disruptions to quality of life. The need for timely accessible information to reduce anxieties was noted in both cohorts.Conclusions This qualitative study found that patients perceived EBRT as being greatly disruptive to their lives. In contrast, the one-off feature of TARGIT-IORT given while they are asleep during surgery gives them the feeling of stamping out the cancer without conscious awareness. These insights can help healthcare staff and policy-makers further justify the incorporation of the treatment favoured by these patient perceptions (TARGIT-IORT) more widely in routine practice. Further research is planned to explore TARGIT-IORT in more diverse populations and in the 35 countries where it is an established treatment option.

ABSTRACT The global burden of infections due to the pathogenic fungus Cryptococcus is substantial in persons with low CD4+ T-cell counts. Previously, we deleted three chitin deacetylase genes from Cryptococcus neoformans to create a chitosan-deficient, avirulent strain, designated as cda1∆2∆3∆, which, when used as a vaccine, protected mice from challenge with virulent C. neoformans strain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8+ T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4+ T cells. Moreover, CD4+ T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4+ T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4+ T cells after vaccination but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in interferon-γ (IFNγ), tumor necrosis factor alpha (TNFα), or interleukin (IL)-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4+ T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8+ T cells are dispensable, IFNγ and CD4+ T cells have overlapping roles in generating protective immunity prior to cda1∆2∆3∆ vaccination. However, once vaccinated, protection becomes less dependent on CD4+ T cells, suggesting a strategy for vaccinating HIV+ persons prior to loss of CD4+ T cells.IMPORTANCEThe fungus Cryptococcus neoformans is responsible for >100,000 deaths annually, mostly in persons with impaired CD4+ T-cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain of C. neoformans, designated as cda1∆2∆3∆. When used as a vaccine, cda1∆2∆3∆ protects mice against a subsequent challenge with a virulent C. neoformans strain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8+ T cells were dispensible, protection was lost in mice genetically deficient in CD4+ T cells and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4+ T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4+ T cells following vaccination, suggesting a strategy to protect persons who are at risk of future CD4+ T-cell dysfunction.

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p

The main aim of this present study was to compare the effect of a flywheel hip extension exercise versus a traditional gravity-dependent exercise on hamstring strength. Twenty U-20 male soccer players volunteered to participate in the study. None had experience with flywheel inertia training, but all had a minimum of 12 months traditional resistance training experience. The participants were randomly assigned to two groups: the flywheel Romanian deadlift and traditional Romanian deadlift groups. Resistance training was performed twice a week for six weeks. Both groups performed four sets of six working repetitions, with the flywheel group performing two extra submaximal pre-repetitions at a low intensity to initiate the rotational force of the flywheel. A significant main effect of time was found for both eccentric strength (p = 0.006) and 3RM (p < 0.001) tests. There was a significant time-by-group interaction for 3RM (p = 0.02) but not for eccentric strength (p = 0.18). Post hoc analyses showed a significant increase in eccentric hamstring strength at the end of the intervention compared to baseline in the flywheel group (13% change, 37 N, p = 0.03, g = 0.51) but not in the traditional group (5% change,14 N, p = 0.282, g = 0.18). Both groups showed significant increases in 3RM Romanian deadlift (flywheel group: 18% change,19 kg, p = < .001, g = 1.07; traditional group: 28 % change, 26 kg, p = < .001, g = 0.99). This study highlights the beneficial use of flywheel training for optimising hamstring strength adaptation. Although both groups showed similar improvements in the 3RM Romanian deadlift, the flywheel group showed superior eccentric strength improvements.

The value of students developing the capacity to accurately judge the quality of their work and that of others has been widely studied and recognized in higher education literature. To date, much of the research and commentary on evaluative judgment has been theoretical and speculative in nature, focusing on perceived benefits and proposing strategies seen to hold the potential to foster evaluative judgment. The efficacy of the strategies remains largely untested. The rise of educational tools and technologies that generate data on learning activities at an unprecedented scale, alongside insights from the learning sciences and learning analytics communities, provides new opportunities for fostering and supporting empirical research on evaluative judgment. Accordingly, this paper offers a conceptual framework and an instantiation of that framework in the form of an educational tool called RiPPLE for data-driven approaches to investigating the enhancement of evaluative judgment. Two case studies, demonstrating how RiPPLE can foster and support empirical research on evaluative judgment, are presented.

Abstract Over-consumption of fructose in adults and children has been linked to increased risk of non-alcoholic fatty liver disease (NAFLD). Recent studies have highlighted the effect of fructose on liver inflammation, fibrosis, and immune cell activation. However, little work summarizes the direct impact of fructose on macrophage infiltration, phenotype, and function within the liver. We demonstrate that chronic fructose diet decreased Kupffer cell populations while increasing transitioning monocytes. In addition, fructose increased fibrotic gene expression of collagen 1 alpha 1 (Col1a1) and tissue metallopeptidase inhibitor 1 (Timp1) as well as inflammatory gene expression of tumor necrosis factor alpha (Tnfa) and expression of transmembrane glycoprotein NMB (Gpnmb) in liver tissue compared to glucose and control diets. Single cell RNA sequencing (scRNAseq) revealed fructose elevated expression of matrix metallopeptidase 12 (Mmp12), interleukin 1 receptor antagonist (Il1rn), and radical S-adenosyl methionine domain (Rsad2) in liver and hepatic macrophages. In vitro studies using IMKC and J774.1 cells demonstrated decreased viability when exposed to fructose. Additionally, fructose increased Gpnmb, Tnfa, Mmp12, Il1rn, and Rsad2 in unpolarized IMKC. By mass spectrometry, C13 fructose tracing detected fructose metabolites in glycolysis and the pentose phosphate pathway (PPP). Inhibition of the PPP further increased fructose induced Il6, Gpnmb, Mmp12, Il1rn, and Rsad2 in nonpolarized IMKC. Taken together, fructose decreases cell viability while upregulating resolution and anti-inflammatory associated genes in Kupffer cells.

The main aim of this paper is to provide an account of Leibniz’s engagement with the doctrine of cosmic dualism in his Theodicy, i.e., the view that there are two distinct fundamental principles that are responsible for the existence of the created world, one good and the other evil. Leibniz’s discussion is primarily a response to arguments in favour of cosmic dualism that he finds in the writings of Pierre Bayle. However, in addition, he presents a genealogical argument that appears to be intended to provide reasons to reject the view. The paper also contains a critical discussion of Leibniz’s case, and finishes by drawing attention to some issues which arise that are worthy of further consideration.

Introduction: Coronavirus disease 2019 (COVID-19) has impacted researchers' ability to continue to deliver HIV prevention and treatment interventions face to face. Although telehealth has been an important strategy to maintain research operations during the current pandemic, participants at increased risk of or living with HIV are often at higher risk of also experiencing poverty, housing instability, and other challenges that may present obstacles to successful remote delivery. Methods: We provide descriptions of remote adaptations to two randomized controlled efficacy trials of behavioral interventions for primary and secondary HIV prevention with descriptive enrollment and retention data. Results and Conclusions: Best practices for implementing telemedicine and e-health procedures are discussed, including procedures for addressing remote participation barriers (economic, health literacy, etc.) and other challenges, such as building rapport and staff support (NCT03092531 and NCT03175159).