Association of Daily Body Temperature, White Blood Cell Count, and C-reactive Protein With Mortality and Persistent Bacteremia in Patients With Staphylococcus Aureus Bacteremia: A Post Hoc Analysis of the CAMERA2 Randomized Clinical Trial

Introduction: Classification of patients with Staphylococcus aureus bacteremia as complicated versus uncomplicated is based on a combination of clinical and microbiologic variables. Whether daily body temperature and common laboratory tests such as C-reactive protein (CRP) and white blood cell (WBC) can improve risk stratification algorithms is unclear. Methods: We conducted a post hoc secondary analysis of the CAMERA2 trial, which enrolled hospitalized adult patients with methicillin-resistant S aureus bacteremia and prospectively collected daily body temperature and peripheral blood WBC and CRP. We evaluated the prognostic relevance of each parameter by calculating crude and adjusted odds ratios for 90-day all-cause mortality comparing patients with the abnormal parameter of interest versus those with normal parameters on each day of illness. Results: A total of 345 patients were included in this analysis, of whom 63 (18.3%) died within 90 days. Fever (body temperature ≥38.0 °C) was associated with increased odds of 90-day mortality from day 4 and onwards. Fever later in the illness course was associated with higher adjusted odds of mortality (8.78; 95% confidence interval, 2.78-27.7 on day 7 vs adjusted odds ratio 3.70; 95% CI, 1.58-8.67 on day 4). In contrast, CRP and abnormal WBC count did not demonstrate a consistent or temporal association with mortality. Conclusions: Persistent fever after 72 hours is associated with increased mortality in patients with methicillin-resistant S aureus bacteremia, supporting recommendations that this should be kept as a criterion for classifying patients as either "high-risk"or "complicated."Within this dataset, there was limited additional predictive value in WBC or CRP

Managing indoor respiratory infection risks with Facilities Management Interventions

© 2025 Yan ZhangThe COVID-19 pandemic reveals that the hazard of respiratory viruses was a secondary consideration in the design, development, construction, and management of public and commercial buildings. An extensive literature review established the link between Facilities Management (FM) and respiratory infection control and identified the research gaps in this interdisciplinary area, including the lack of empirical studies on Facilities Management Intervention (FMI) decision-making and occupant behaviour change (OBC) related to respiratory infection control and application of multi-route dose-response models in FMI outcomes assessment. This thesis adopts a mixed method and includes three studies to address the research question: “How can we manage indoor respiratory infection control with FMIs?” In Study 1, 41 semi-structured interviews were conducted with facilities managers and key stakeholders to explore FMI practices, outcomes, and decision-making, as well as observed OBC in post-COVID Melbourne. Study 2 collected 2129 survey responses from building occupants based in 90 buildings to explore occupant risk perceptions (RP) and OBC. Study 3 developed an interactive application named FMI Outcomes Calculator (FMIOC), which integrates the latest research on indoor respiratory transmission mechanisms and risk assessment methods, as well as insights from the empirical findings (Study 1 and Study 2). Study 1 provided empirical evidence on FMI practices and identified measurement of FMI outcomes from economic, health, environmental, and social perspectives. It found that interventions on indoor air quality (IAQ) were more influenced by internal drivers from the organisations rather than compliance pressures, revealing IAQ policy gaps in Australia. Moreover, the interviews revealed the challenges practitioners faced in understanding respiratory transmission mechanisms and quantifying FMI outcomes, which pointed to the need for data-based tools. Study 2 identified determinants for RP and OBC towards each transmission route. The survey findings highlighted the role of occupant trust and revealed changes in occupants' expectations about IAQ and individual space. Additionally, Study 2 established evidence-based OB parameters for respiratory infection risk assessment. These findings have important management implications for FM in respiratory infection control and post-COVID workplace management. Study 3 developed FMIOC, which enables users to calculate risk outcomes in multiple transmission routes, as well as additional energy consumption and costs from combined FMIs. The app can help users understand the multi-route transmission mechanism, identify the dominating transmission route in various scenarios, and conduct scenario analysis under different virus, community prevalence, and OB scenarios for FMI decision-making. This thesis has made significant empirical and practical contributions to FM and respiratory infection control. It provides evidence-based insights on FMI practice, outcomes, decision-making, occupant RP and OBC regarding respiratory infection control. It also provides a new application for FMI outcomes assessment. This thesis serves as a new approach for managing respiratory infections with FMIs

Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: Part 2—Ex vivo imaging: Added value and acquisition

The value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher SNR and spatial resolution compared to in vivo studies, and enabling more advanced diffusion contrasts for improved microstructure and connectivity characterization. Another major advantage of ex vivo dMRI is the direct comparison with histological data, as a crucial methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work represents "Part 2" of a three-part series of recommendations and considerations for preclinical dMRI. We describe best practices for dMRI of ex vivo tissue, with a focus on the value that ex vivo imaging adds to the field of dMRI and considerations in ex vivo image acquisition. We first give general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in specimens and models and discuss why some may be more or less appropriate for different studies. We then give guidelines for ex vivo protocols, including tissue fixation, sample preparation, and MR scanning. In each section, we attempt to provide guidelines and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should lie. An overarching goal herein is to enhance the rigor and reproducibility of ex vivo dMRI acquisitions and analyses, and thereby advance biomedical knowledge

Exploring the Implementation of Cognitive Screening in First-Episode Psychosis Settings: The CogScreen Implementation Study

Aim: Accurate and appropriate cognitive screening can significantly enhance early psychosis care, yet no screening tools have been validated for the early psychosis population and little is known about current screening practices, experiences, or factors that may influence implementation. CogScreen is a hybrid type 1 study aiming to validate two promising screening tools with young people with first episode psychosis (primary aim) and to understand the context for implementing cognitive screening in early psychosis settings (secondary aim). This protocol outlines the implementation study, which aims to explore the current practices, acceptability, feasibility and determinants of cognitive screening in early psychosis settings from the perspective of key stakeholders. Methods: Young people with first episode psychosis (n = 350), caregivers (minimum n = 10) and service providers (minimum n = 12) will be recruited from primary and specialist early psychosis services in Melbourne, Adelaide and Sydney, Australia. Two implementation science frameworks will inform data collection and analysis: the Theoretical Framework of Acceptability and the Consolidated Framework for Implementation Research. A mixed-methods design will be employed to collect and analyse data from questionnaires with young people, interviews with all stakeholder groups, and administrative processes. Quantitative data will be analysed using descriptive statistics. Qualitative data will be analysed through content analysis using deductive and inductive coding. Results and Discussion: This protocol paper presents the rationale and methods for the CogScreen implementation study. Conclusion: Together with accuracy findings, results from the implementation study will provide insights about the practices, experiences, enablers and barriers to cognitive screening in early psychosis services

Application of virtual reality to assess thermal, visual perception, and users' adaptive behaviors for sedentary activities

VR technology has shown to effectively explore the psychological and physiological effects of the built environment on users. This study investigates multisensory integration using VR technology, focusing on same-modal and cross-modal effects during sedentary activities. A survey-based approach was employed to collect data from participants within a controlled climate setting. A virtual replica of Monash Makerspace was developed to assess its thermal, visual impact, and behavioral responses. The results revealed significant differences in the same modal effects, however, no significant differences in cross-modal effects were observed regarding the influence of visual stimuli on thermal sensations, preferences, and comfort. Conversely, cross-modal effects of thermal conditions on visual perceptions demonstrated significant differences in visual sensation and comfort, except for visual preferences. Furthermore, there was no significant difference in physiological responses between IVEs and among thermal conditions. The findings indicate that warm yellow lights are only suitable and comfortable for users during cool temperatures. In contrast, cool white light was most preferred and comfortable across conditions for users. A small number of participants preferred the lighting in between the two visual scenarios evaluated. The insight can inform the design of new buildings and retrofitting of existing ones to accommodate user comfort, particularly given that Australian buildings maintain indoor thermal conditions between 18ºC to 30ºC across seasons. Nevertheless, the study has some limitations, including that participants were exposed to these visual scenarios and thermal conditions for a short duration, which does not represent the long-term adaptation effects. Also, the study was conducted using students within the age bracket of 18-40 years, limiting the generalizability of the findings to younger or older groups

Laboratory performance assessment of low-cost water level sensor for field monitoring in the tropics

As Water Sensitive Urban Design (WSUD) is a key strategy in integrated urban water management worldwide, there is a need for robust monitoring of WSUD systems. Being economical and flexible for operation and communication, low-cost sensor systems show great potential to mainstream digital water management. Yet, such systems are insufficiently tested, casting doubt on the reliability of their measurements. Here, we document a robust testing approach for a pressure transducer water level low-cost sensor (KIT0139) and a traditional sensor (OTT PLS) in both laboratory and field conditions. We tested six different devices under three temperatures relevant to tropical climate: 25, 30, 35 °C and proposed a field calibration approach. Results reveal that the low-cost sensors were robust as the six individual devices performed consistently under different testing conditions. After calibration, low-cost sensors provided sufficient accuracy (±10mm) and precision for water levels more than 0.05m. While varying water flow direction did not significantly influence the performance, we showed that calibration should be done for individual devices. In addition, large (>5 °C) variations in water temperature and varying wet/dry conditions may also influence the performance of the low-cost sensors. The field calibration approach was validated in a 3-month experiment, confirming that this model of low-cost sensor can effectively replace traditional sensors in the field in tropical climates. Our study confirms that systematic and thorough testing is needed for low-cost sensors systems to realize their full potential for scientific-grade applications. We provide practical recommendations to conduct such testing from the laboratory to the field

FABP7 in Hepatic Macrophages Promotes Fibroblast Activation and CD4+ T-Cell Migration by Regulating M2 Polarization During Liver Fibrosis

Hepatic macrophages respond to various microenvironmental signals and play a central role in maintaining hepatic homeostasis, dysregulation of which leads to various liver diseases. Fatty acid-binding protein 7 (FABP7), an intracellular lipid chaperone for polyunsaturated fatty acids (PUFAs), is highly expressed in liver macrophages. However, the mechanisms by which FABP7 regulates hepatic macrophage activation remain unclear. Therefore, we aimed to elucidate the mechanisms underlying the effects of FABP7 on the functions of hepatic macrophages in metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis models. In this study, we found that FABP7-deficient macrophages exhibited impaired M2 polarization, which reduced the fibrotic response of myofibroblasts and CD4+ T-cell infiltration into the liver tissues in a carbon tetrachloride (CCl4)-induced hepatic fibrosis model. In vitro, FABP7-deficient macrophages exhibited decreased levels of peroxisome proliferator-activated receptor (PPAR)-γ and its target genes, including C-C motif chemokine ligand (CCL)-17 and transforming growth factor-β (TGF-β), compared to the wild-type (WT) macrophages post-interleukin (IL)-4 stimulation. However, these effects were inhibited by a PPARγ inhibitor. IL-4-stimulated WT macrophages also promoted CD4+ T-cell migration and hepatic fibroblast (TWNT-1 hepatic stellate cell [HSC]) activation, indicated by increased mRNA levels of actin alpha 2, smooth muscle (ACTA2), and collagen type I alpha 1 (COL1A1); however, these effects were inhibited in FABP7-deficient macrophages. Overall, FABP7 in hepatic macrophages modulated the crosstalk between hepatic fibroblasts and T cells by regulating M2 polarization. Therefore, regulation of hepatic macrophage function by FABP7 is a potential therapeutic target for liver fibrosis

Early mucosal responses following a randomised controlled human inhaled infection with attenuated Mycobacterium bovis BCG

The development of an effective vaccine against Mycobacterium tuberculosis is hampered by an incomplete understanding of immunoprotective mechanisms. We utilise an aerosol human challenge model using attenuated Mycobacterium bovis BCG, in BCG-naïve UK adults. The primary endpoint of this study (NCT03912207) was to characterise the early immune responses induced by aerosol BCG infection, the secondary endpoint was to identify immune markers associated with in-vitro protection. Blinded volunteers were randomised to inhale 1 × 107 CFU aerosolised BCG or 0.9% saline (20:6); and sequentially allocated to bronchoscopy at day 2 or 7 post-inhalation (10 BCG, 3 saline each timepoint). In the bronchoalveolar lavage post-aerosol BCG infection, there was an increase in frequency of eosinophils, neutrophils, NK cells and Donor-Unrestricted T cells at day 7, and the frequency of antigen presenting cells decreased at day 7 compared with day 2. The frequency of interferon-gamma+ BCG-specific CD4+ T cells increased in the BAL and peaked in the blood at day 7 post-BCG infection compared to day 2. BAL cells at day 2 and day 7 upregulated gene pathways related to phagocytosis, MHC-II antigen loading, T cell activation and proliferation. BCG's lack of key virulence factors and its failure to induce granulomas, may mean the observed immune responses do not fully recapitulate Mycobacterium tuberculosis infection. However, human infection models can provide unique insights into early immune mechanisms, informing vaccine design for complex pathogens

Business Model Innovation: A Spatiotemporal Exploration

© 2025 Nermin AzabagicInterest in Business Model Innovation (BMI) has flourished in the last two decades, helping to establish it as a key concept, in both industry practice, and academic research. BMI is a complex, multifaceted phenomenon. This PhD thesis examines BMI as a process in which a firm deliberately makes important changes to key elements of its existing business model or develops an entirely new one. The PhD research is specifically focusing on the actors, activities, and interactions involved, using a spatiotemporal perspective to explore relevant contextual (spatial) and temporal factors shaping BMI. By means of a systematic review of the field, this PhD research examines the key definitions and concepts related to BMI, taking stock of the current state of BMI literature. As a result of the review, a taxonomy of spatiotemporally related boundary conditions is proposed. By means of qualitative research methods, the PhD research furthermore explored the process of BMI in established firms. Prior research has found that established firms find BMI challenging, due to cognitive constraints including path-dependency, industry dominant logic, and managers’ bounded rationality. Hence, a focus on established firms can add insights on how these challenges are addressed during BMI. Partnering with IBM Consulting, this PhD research examined, first, how strategy and design consultants work with established firms to undertake BMI. This research finds that activities inspired from the temporal categories of the present and near/distant future can address actors’ cognitive constraints and help unleash creative leaps needed for BMI. These insights contribute theoretically to the cognitive and temporal perspective on BMI. For managers, a process model is provided, with temporally ordered activities, which can help facilitate BMI. This thesis also explored how human actors interface with non-human actors, i.e. GenAI tools, in the context of BMI. A study of strategy consultants using GenAI for BMI uncovered a set of tensions when working with GenAI, including those related to confidence, trust, reliance and perceptions of value. Applying a paradox theory lens, this research identified an overarching paradoxical tension between automation and augmentation, which unfolds at the individual and task level. Consultants tended to navigate a precarious balance between gaining value from automation and/or augmentation, while protecting their own value within the organisation, and with their clients. Findings highlight a range of paradoxical management strategies, which have potential to lead to either vicious, or virtuous cycles. These insights contribute to paradox theory, demonstrating a multi-level paradoxical tension between automation and augmentation, while offering managers insights on how to manage the tensions in the fast-evolving world of GenAI. The overarching contribution of this PhD thesis is to illuminate a range of previously under-explored aspects of the BMI process in established firms, including actors, activities and interactions, through a spatiotemporal perspective. Overall findings indicate a need for elevating the focus on the future as a temporal category; deeper exploration of the balance between creative and analytical activities; and further examination of GenAI’s evolving role in BMI. Lastly, this research suggests that paradox theory may be a helpful frame to study the many tensions embedded in the complex undertaking that is BMI