Designing Rigorous and Efficient Clinical Utility Studies for Early Detection Biomarkers.

Before implementing a biomarker in routine clinical care, it must demonstrate clinical utility by leading to clinical actions that positively affect patient-relevant outcomes. Randomly controlled early detection utility trials, especially those targeting mortality endpoint, are challenging due to their high costs and prolonged duration. Special design considerations are required to determine the clinical utility of early detection assays. This commentary reports on discussions among the National Cancer Institute's Early Detection Research Network investigators, outlining the recommended process for carrying out single-organ biomarker-driven clinical utility studies. We present the early detection utility studies in the context of phased biomarker development. We describe aspects of the studies related to the features of biomarker tests, the clinical context of endpoints, the performance criteria for later phase evaluation, and study size. We discuss novel adaptive design approaches for improving the efficiency and practicality of clinical utility trials. We recommend using multiple strategies, including adopting real-world evidence, emulated trials, and mathematical modeling to circumvent the challenges in conducting early detection utility trials.

An unusual case of Herbaspirillum huttiense bacteraemia in a haemodialysis patient.

Herbaspirillum spp. is a common environmental bacterium usually found in soil, plant roots, and water. It is rarely associated with infection in immunocompromised patients, and rarely reported infections in immunocompetent patients. We report the first case of a Herbaspirillum huttiense bacteraemia in a non-neutropenic home haemodialysis patient. A 57-year-old male presented to our hospital with a 3-day history of malaise, fevers, rigours, and anorexia following dialysis through his central line. On examination, he was pyrexic (temperature 38.7°C) with splinter haemorrhages noted, but no other signs of infection were present. Blood cultures revealed a polymicrobial infection, with Serratia liquefaciens and Corynebacterium jeikeium isolated from the central line and Herbaspirillum sp. was isolated from both the central line and a peripheral culture. A later peripheral blood culture following central line removal isolated Herbaspirillum huttiense. Regular biological testing of his home water supply and dialysate detected no colony forming units of non-fermenting gram-negative bacilli. He was initially treated with ceftriaxone and vancomycin initially, followed by ertapenem and vancomycin. Intravenous antibiotics were ceased following 5 days after central line removal and he made an uneventful recovery.

Potential association of SULT2A1 and ABCG2 variant alleles with increased risk for palbociclib toxicity.

Aim: This study evaluated associations between CYP3A4*22 and variants in other pharmacogenes (CYP3A5, SULT2A1, ABCB1, ABCG2, ERCC1) and the risk for palbociclib-associated toxicities. Materials & methods: Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively. Results: No significant associations were found for CYP3A4*22, CYP3A5*3, ABCB1_rs1045642, ABCG2_rs2231142, ERCC1_rs3212986 and ERCC1_rs11615. Homozygous variant carriers of SULT2A1_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, p = 0.042). ABCG2_rs2231137 variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, p = 0.052). Conclusion: Once validated, SULT2A1 and ABCG2 variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.

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An external facilitation case study analysis of an implementation trial of FLOW: A program for improving the transition of patients with mental health disorders back to primary care.

FLOW (not an acronym) is a program that aims to improve mental health (MH) access using an algorithm that extracts electronic medical record data to identify recovered or stabilized MH patients who may be eligible to transition to primary care. The purpose of this case study was to describe and understand the factors that contributed to success or struggles in implementing FLOW. We conducted a posthoc evaluation of four health care sites implementing FLOW, using a mixed-method formal case study analysis. Qualitative data included written process notes, teleconference minutes, and interviews with internal facilitators (IF), MH providers, and patients who were transitioned. The external facilitation team also examined the degree to which IF characteristics matched suggested criteria. Quantitative data included discharge percentages and the percentage of providers who transitioned ≥ three patients during implementation. Sites were considered successful if they: (a) discharged ≥ 3% of their unique MH patients and (b) had a preponderance of patients who were satisfied with their MH to primary care transition. This article discusses two successful and two struggling FLOW sites based on these and other criteria and the factors that contributed to these outcomes. These case study findings increased understanding of how to successfully implement FLOW. The importance of shared decision making, selection of the IF, role definition, as well as leadership and organizational support are key elements in fostering appropriate transitions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Description of census-tract-level social determinants of health in cancer surveillance data.

BACKGROUND: Disparities in cancer incidence, stage at diagnosis, and mortality persist by race, ethnicity, and many other social determinants, such as census-tract-level socioeconomic status (SES), poverty, and rurality. Census-tract-level measures of these determinants are useful for analyzing trends in cancer disparities. METHODS: The purpose of this paper was to demonstrate the availability of the Surveillance, Epidemiology, and End Results Program's specialized census-tract-level dataset and provide basic descriptive cancer incidence, stage at diagnosis, and survival for 8 cancer sites, which can be screened regularly or associated with infectious agents. We present these analyses according to several census-tract-level measures, including the newly available persistent poverty as well as SES quintile, rurality, and race and ethnicity. RESULTS: Census tracts with persistent poverty and low SES had higher cancer incidence rates (except for breast and prostate cancer), higher percentages of cases diagnosed with regional or distant-stage disease, and lower survival than non-persistent-poverty and higher-SES tracts. Outcomes varied by cancer site when analyzing based on rurality as well as race and ethnicity. Analyses stratified by multiple determinants showed unique patterns of outcomes, which bear further investigation. CONCLUSIONS: This article introduces the Surveillance, Epidemiology, and End Results specialized dataset, which contains census-tract-level social determinants measures, including persistent poverty, rurality, SES quintile, and race and ethnicity. We demonstrate the capacity of these variables for use in producing trends and analyses focusing on cancer health disparities. Analyses may inform interventions and policy changes that improve cancer outcomes among populations living in disadvantaged areas, such as persistent-poverty tracts.

A Protocol to Determine Circadian Phase by At-Home Salivary Dim Light Melatonin Onset Assessment.

Internal circadian phase assessment is increasingly acknowledged as a critical clinical tool for the diagnosis, monitoring, and treatment of circadian rhythm sleep-wake disorders and for investigating circadian timing in other medical disorders. The widespread use of in-laboratory circadian phase assessments in routine practice has been limited, most likely because circadian phase assessment is not required by formal diagnostic nosologies, and is not generally covered by insurance. At-home assessment of salivary dim light melatonin onset (DLMO, a validated circadian phase marker) is an increasingly accepted approach to assess circadian phase. This approach may help meet the increased demand for assessments and has the advantages of lower cost and greater patient convenience. We reviewed the literature describing at-home salivary DLMO assessment methods and identified factors deemed to be important to successful implementation. Here, we provide specific protocol recommendations for conducting at-home salivary DLMO assessments to facilitate a standardized approach for clinical and research purposes. Key factors include control of lighting, sampling rate, and timing, and measures of patient compliance. We include findings from implementation of an optimization algorithm to determine the most efficient number and timing of samples in patients with Delayed Sleep-Wake Phase Disorder. We also provide recommendations for assay methods and interpretation. Providing definitive criteria for each factor, along with detailed instructions for protocol implementation, will enable more widespread adoption of at-home circadian phase assessments as a standardized clinical diagnostic, monitoring, and treatment tool.

Impact of SPY Fluorescence Angiography on Incidence of Ureteroenteric Stricture After Urinary Diversion.

PURPOSE: Ureteroenteric strictures (UESs) are a common and morbid complication of radical cystectomy and urinary diversions. UES occurs in 4% to 25% of all patients undergoing urinary diversion, and anastomotic ischemia is implicated in stricture formation. SPY fluorescence angiography is a technology that can be employed during open surgery that allows for evaluation of ureteral perfusion. MATERIALS AND METHODS: We performed a prospective single-institution study of intraoperative use of SPY for ureteral assessment with a primary outcome of UES incidence compared with a cohort of historic controls prior to the use of SPY during urinary diversion at our institution. Chart abstraction was conducted to determine the presence of confirmed stricture in these patients, defined as endoscopic diagnosis or definitive imaging findings. Statistical analysis was performed using χ2 test for UES incidence. Demographics characteristics were analyzed with Wilcoxon rank sum test and χ2 test. RESULTS: A total of 332 patients underwent urinary diversion during the study period. UES occurred in 31 of 277 patients (11.1%) in the control group compared with 1 of 55 patients (1.8%) enrolled in the SPY arm (P = .03). The per-ureter UES rate was 6.7% (33/582) in the control group compared with 0.9% (1/107) in the SPY group. Median follow-up in the SPY group was 17.5 months and 58.6 months in the control group. Median Charlson Comorbidity Index was 5 in the SPY group and 4 in the control group. There were no other significant demographic differences between the study groups. CONCLUSIONS: SPY fluorescent angiography can be used during open urinary diversion to ensure perfusion to ureteroenteric anastomosis. Our single-institution study demonstrates a decreased incidence of UES when ureteral perfusion assessment is performed. CLINICAL TRIAL REGISTRATION NO.: NCT05022199.

Type I interferon governs immunometabolic checkpoints that coordinate inflammation during Staphylococcal infection.

Macrophage metabolic plasticity is central to inflammatory programming, yet mechanisms of coordinating metabolic and inflammatory programs during infection are poorly defined. Here, we show that type I interferon (IFN) temporally guides metabolic control of inflammation during methicillin-resistant Staphylococcus aureus (MRSA) infection. We find that staggered Toll-like receptor and type I IFN signaling in macrophages permit a transient energetic state of combined oxidative phosphorylation (OXPHOS) and aerobic glycolysis followed by inducible nitric oxide synthase (iNOS)-mediated OXPHOS disruption. This disruption promotes type I IFN, suppressing other pro-inflammatory cytokines, notably interleukin-1ß. Upon infection, iNOS expression peaks at 24 h, followed by lactate-driven Nos2 repression via histone lactylation. Type I IFN pre-conditioning prolongs infection-induced iNOS expression, amplifying type I IFN. Cutaneous MRSA infection in mice constitutively expressing epidermal type I IFN results in elevated iNOS levels, impaired wound healing, vasculopathy, and lung infection. Thus, kinetically regulated type I IFN signaling coordinates immunometabolic checkpoints that control infection-induced inflammation.

Patient Satisfaction with a Novel Tele-Cystoscopy Model: Expanding Access to Bladder Cancer Surveillance for Rural Patients.

Background: Tele-cystoscopy involves trained advanced practice providers performing cystoscopy with real-time interpretation by an urologist. The goal of this externally validated care model is to expand the availability of cystoscopy to underserved rural areas. Herein we report on population demographics and describe the socioeconomic benefits of tele-cystoscopy for bladder cancer surveillance. Methods: Using an IRB-approved protocol, patients were consented for dual, sequential cystoscopy wherein they experienced a standard-of-care cystoscopy along with tele-cystoscopy. Patients completed a questionnaire that contained both subjective and objective health and socioeconomic-related questions as well as a satisfaction survey. Patients were also probed about factors associated with transportation to their cystoscopy appointments including gasoline costs, travel time, and time off work. Using the Distressed Community Index, patients were ascribed an economic resource category ranging from prosperous to distressed. Results: In total, 48 patients with a mean age of 55 completed surveys after completing dual cystoscopies. Thirteen patients (27%) were uninsured and 10 patients (20%) had Medicaid as primary insurance. The tele-cystoscopy clinic saved patients an average of 235 miles and 434 min of travel time. In total, 82% of patients resided in a distressed community indicating fewer economic resources. Satisfaction results showed a mean score of 31.38 (out of 32). Conclusions: Patients were satisfied with tele-cystoscopy, noting increased access to health care and fewer disruptions impacting bladder cancer surveillance. Tele-cystoscopy may be a viable option to expand access and improve adherence to guidelines for bladder cancer surveillance, particularly benefiting patients in rural areas and those of lower socioeconomic status.

Explainable Artificial Intelligence for Early Prediction of Pressure Injury Risk.

BACKGROUND: Hospital-acquired pressure injuries (HAPIs) have a major impact on patient outcomes in intensive care units (ICUs). Effective prevention relies on early and accurate risk assessment. Traditional risk-assessment tools, such as the Braden Scale, often fail to capture ICU-specific factors, limiting their predictive accuracy. Although artificial intelligence models offer improved accuracy, their "black box" nature poses a barrier to clinical adoption. OBJECTIVE: To develop an artificial intelligence-based HAPI risk-assessment model enhanced with an explainable artificial intelligence dashboard to improve interpretability at both the global and individual patient levels. METHODS: An explainable artificial intelligence approach was used to analyze ICU patient data from the Medical Information Mart for Intensive Care. Predictor variables were restricted to the first 48 hours after ICU admission. Various machine-learning algorithms were evaluated, culminating in an ensemble "super learner" model. The model's performance was quantified using the area under the receiver operating characteristic curve through 5-fold cross-validation. An explainer dashboard was developed (using synthetic data for patient privacy), featuring interactive visualizations for in-depth model interpretation at the global and local levels. RESULTS: The final sample comprised 28 395 patients with a 4.9% incidence of HAPIs. The ensemble super learner model performed well (area under curve = 0.80). The explainer dashboard provided global and patient-level interactive visualizations of model predictions, showing each variable's influence on the risk-assessment outcome. CONCLUSION: The model and its dashboard provide clinicians with a transparent, interpretable artificial intelligence-based risk-assessment system for HAPIs that may enable more effective and timely preventive interventions.

BASSA: New software tool reveals hidden details in visualisation of low-frequency animal sounds.

The study of animal sounds in biology and ecology relies heavily upon time-frequency (TF) visualisation, most commonly using the short-time Fourier transform (STFT) spectrogram. This method, however, has inherent bias towards either temporal or spectral details that can lead to misinterpretation of complex animal sounds. An ideal TF visualisation should accurately convey the structure of the sound in terms of both frequency and time, however, the STFT often cannot meet this requirement. We evaluate the accuracy of four TF visualisation methods (superlet transform [SLT], continuous wavelet transform [CWT] and two STFTs) using a synthetic test signal. We then apply these methods to visualise sounds of the Chagos blue whale, Asian elephant, southern cassowary, eastern whipbird, mulloway fish and the American crocodile. We show that the SLT visualises the test signal with 18.48%-28.08% less error than the other methods. A comparison between our visualisations of animal sounds and their literature descriptions indicates that the STFT's bias may have caused misinterpretations in describing pygmy blue whale songs and elephant rumbles. We suggest that use of the SLT to visualise low-frequency animal sounds may prevent such misinterpretations. Finally, we employ the SLT to develop 'BASSA', an open-source, GUI software application that offers a no-code, user-friendly tool for analysing short-duration recordings of low-frequency animal sounds for the Windows platform. The SLT visualises low-frequency animal sounds with improved accuracy, in a user-friendly format, minimising the risk of misinterpretation while requiring less technical expertise than the STFT. Using this method could propel advances in acoustics-driven studies of animal communication, vocal production methods, phonation and species identification.

Deconstructing nursing's paradoxical relationship with the concept of complexity.

Although nursing seems to understand itself and its practice as complex, the literature is less clear about what this actually means. While complexity is discussed as an attribute of nursing, it is also suggested that complexity in nursing remains misunderstood and poorly articulated, is devalued, is not considered as a measure of health outcomes and remains invisible. Despite the overarching lack of a definition, some nurse scholars have conceptualized complexity as a complex intervention. For these authors, complexity becomes a complex intervention defined as that which is composed of component parts interacting in a variety of ways that influence the delivery of and outcomes of health-related interventions for populations. Conceptualizing complexity as a complex intervention forces nursing to embrace and adopt a received interpretation of complexity as expressed through complexity theory and complexity science. While complexity theory may afford us some tools for thinking about complexity, when we deconstruct nursing complexity to explicitly determinate and quantifiable tasks, this artificially narrowed orientation to complexity reveals an oversimplified explanation of the complexities associated with nursing and serves to blind us to its real qualities. Through a consideration of complexity from a Western philosophical tradition, I demonstrate that when nursing adopts the received interpretation of complexity as a complex intervention, this perspective on complexity contains nursing epistemologically and ontologically. I offer an extended conceptualization of complexity framed upon the consideration that nurses assume complexity and do not reduce it; that nurses have the capacity to not be paralysed by complexity and have developed logics to mobilize it in productive ways. Mobilizing complexity through navigating paradox and contradiction shapes an orientation to complexity that embraces an extended epistemology. This extended epistemology is characterized by a 'yes/and' mindset that expresses the dynamic and generative relationship between forms of knowledge which reflects complexity that characterizes nursing.

Laboratory Animal Models for Rift Valley Fever Virus Disease.

Rift Valley fever virus (RVFV) is an arboviral pathogen of clinical and agricultural relevance. The ongoing development of targeted RVFV prophylactics and therapeutics is overwhelmingly dependent on animal models due to both natural, that is, sporadic outbreaks, and structural, for example, underresourcing of endemic regions, limitations in accessing human patient samples and cohorts. Elucidating mechanisms of viral pathogenesis and testing therapeutics is further complicated by the diverse manifestations of RVFV disease and the heterogeneity of the host response to infection. In this chapter, we describe major clinical manifestations of RVFV infection and discuss the laboratory animal models used to study each.

DigiTRAC: Qualitative insights from knowledge users to inform the development of a Digital Toolkit for enhancing resilience among multiple sclerosis caregivers.

BACKGROUND: Resilience-promoting resources are critically needed to support positive caregiving experiences for multiple sclerosis (MS) caregivers. A digital toolkit offers a flexible way to access and use evidence-based resources that align with MS caregivers' interests and needs over time. OBJECTIVE: We explored the perspectives of key knowledge users regarding content areas, features, and other considerations to inform an MS caregiver resilience digital toolkit. METHODS: Twenty-two individuals completed a demographic survey as part of this study: 11 MS family caregivers, 7 representatives of organizations providing support services for people with MS and/or caregivers, and 4 clinicians. We conducted nine semi-structured individual interviews and two focus groups. Data were analyzed using content analysis. RESULTS: Participants recommended that a digital toolkit should include content focused on promoting MS caregivers' understanding of the disease, its trajectory and available management options, and enhancing caregiving skills and caregivers' ability to initiate and maintain behaviours to promote their own well-being. Features that allow for tracking and documenting care recipients' and caregivers' experiences, customization of engagement, and connectivity with other sources of support were also recommended. Participants suggested a digital toolkit should be delivered through an app with web browser capabilities accessible on smartphones, tablets, or laptops. They also acknowledged the need to consider how users' previous technology experiences and issues related to accessibility, usability, privacy and security could influence toolkit usage. CONCLUSION: These findings will guide future toolkit development and evaluation. More broadly, this study joins the chorus of voices calling for critical attention to the well-being of MS family caregivers.

IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.

SleepSync: Early Testing of a Personalised Sleep-Wake Management Smartphone Application for Improving Sleep and Cognitive Fitness in Defence Shift Workers.

Shift work, long work hours, and operational tasks contribute to sleep and circadian disruption in defence personnel, with profound impacts on cognition. To address this, a digital technology, the SleepSync app, was designed for use in defence. A pre-post design study was undertaken to examine whether four weeks app use improved sleep and cognitive fitness (high performance neurocognition) in a cohort of shift workers from the Royal Australian Air Force. In total, 13 of approximately 20 shift-working personnel from one base volunteered for the study. Sleep outcomes were assessed using the Insomnia Severity Index (ISI), the Patient-Reported Outcomes Measurement Information System (PROMIS), Sleep Disturbance and Sleep-Related Impairment Scales, the Glasgow Sleep Effort Scale, the Sleep Hygiene Index, and mental health was assessed using the Depression, Anxiety, and Stress Scale-21. Sustained attention was measured using the 3-min Psychomotor Vigilance Task (PVT) and controlled response using the NBack. Results showed significant improvements in insomnia (ISI scores 10.31 at baseline and 7.50 after app use), sleep-related impairments (SRI T-scores 53.03 at baseline to 46.75 post-app use), and healthy sleep practices (SHI scores 21.61 at baseline to 18.83 post-app use; all p < 0.001). Trends for improvement were recorded for depression. NBack incorrect responses reduced significantly (9.36 at baseline; reduced by -3.87 at last week of app use, p < 0.001), but no other objective measures improved. These findings suggest that SleepSync may improve sleep and positively enhance cognitive fitness but warrants further investigation in large samples. Randomised control trials with other cohorts of defence personnel are needed to confirm the utility of this intervention in defence settings.

Movement and Pressure Injury Prevention Care for Nursing Home Residents: Addressing the Nescience.

OBJECTIVE: To compare movement associated with position changes among nursing home residents who remain in lying versus upright positions for more than 2 hours and among residents living with obesity, dementia, or neither condition. METHODS: The authors conducted a descriptive exploratory study using secondary data (N = 934) from the Turn Everyone And Move for Ulcer Prevention (TEAM-UP) clinical trial to examine transient movements (<60 seconds) within prolonged periods of 2 to 5 hours without repositioning. RESULTS: Nursing home residents exhibit significantly more episodic transient movements when upright than lying. Residents with obesity or dementia exhibited similar frequencies of episodic transient movements compared with residents with neither obesity nor dementia. Upright or lying movements were more frequent among residents with obesity than among those with neither obesity nor dementia selectively when prolonged events ranged from 2 to 4 hours. Pairwise comparisons of movement rates among resident subgroups (living with obesity, living with dementia, or neither group) across repositioning intervals showed episodic transient movements were significantly higher across all subgroups for repositioning intervals up to 3 hours when compared with repositioning intervals of greater than 3 hours. CONCLUSIONS: Findings challenge assumptions that nursing home residents are inactive and at risk for prolonged sitting. These preliminary findings, along with TEAM-UP findings where no pressure injuries occurred in up to 5 hours in prolonged positions, support establishing a standard 3-hour repositioning interval with use of high-density mattresses without a negative impact on pressure injury occurrence. There should be caution when considering repositioning intervals greater than 3 hours. Further research is indicated to explore protective effect of episodic transient movements of other subgroups.

Assessment and management of sleep disorders in shift workers: Challenges and considerations for general practice.

BACKGROUND: Shift work is characterised by displaced sleep opportunities and associated sleep disturbance. Shift workers often report sleepiness and other wake time symptoms associated with poor sleep. However, clinical sleep disorders are also prevalent in shift workers. Although prevalence rates are similar or higher in shift workers compared with the general population, help seeking in shift workers with sleep disorders is low. OBJECTIVE: This article aims to provide general practitioners with a contemporary overview of the prevalence rates for sleep disorders in shift workers, to clarify the existing evidence relating to mental and physical health consequences of sleep disorders in shift workers and to highlight the need to consider undiagnosed sleep disorders before attributing sleep-related symptoms solely to work schedules. DISCUSSION: Symptoms of sleep loss associated with shift work overlap with symptoms experienced by individuals living with sleep disorders. Although >40% of middle-aged Australians live with a sleep disorder that requires investigation and management, symptoms in shift workers are often attributed to the work schedule and, as a result, might not be investigated for appropriate diagnosis and treatment. We argue that screening for sleep disorders in shift workers with sleep complaints should be a priority.

Translation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors.

The parasite Toxoplasma gondii persists in its hosts by converting from replicating tachyzoites to latent bradyzoites housed in tissue cysts. The molecular mechanisms that mediate T. gondii differentiation remain poorly understood. Through a mutagenesis screen, we identified translation initiation factor eIF1.2 as a critical factor for T. gondii differentiation. A F97L mutation in eIF1.2 or the genetic ablation of eIF1.2 (∆eif1.2) markedly impeded bradyzoite cyst formation in vitro and in vivo. We demonstrated, at single-molecule level, that the eIF1.2 F97L mutation impacts the scanning process of the ribosome preinitiation complex on a model mRNA. RNA sequencing and ribosome profiling experiments unveiled that ∆eif1.2 parasites are defective in upregulating bradyzoite induction factors BFD1 and BFD2 during stress-induced differentiation. Forced expression of BFD1 or BFD2 significantly restored differentiation in ∆eif1.2 parasites. Together, our findings suggest that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish chronic toxoplasmosis.

Professional regulation in the digital era: A qualitative case study of three professions in Ontario, Canada.

Technology is transforming service delivery and practice in many regulated professions, altering required skills, scopes of practice, and the organization of professional work. Professional regulators face considerable pressure to facilitate technology-enabled work while adapting to digital changes in their practices and procedures. However, our understanding of how regulators are responding to technology-driven risks and the impact of technology on regulatory policy is limited. To examine the impact of technology and digitalization on regulation, we conducted an exploratory case study of the regulatory bodies for nursing, law, and social work in Ontario, Canada. Data were collected over two phases. First, we collected documents from the regulators' websites and regulatory consortiums. Second, we conducted key informant interviews with two representatives from each regulator. Data were thematically analyzed to explore the impact of technological change on regulatory activities and policies and to compare how regulatory structure and field shape this impact. Five themes were identified in our analysis: balancing efficiency potential with risks of certain technological advances; the potential for improving regulation through data analytics; considering how to regulate a technologically competent workforce; recalibrating pandemic emergency measures involving technology; and contemplating the future of technology on regulatory policy and practice. Regulators face ongoing challenges with providing equity-based approaches to regulating virtual practice, ensuring practitioners are technologically competent, and leveraging regulatory data to inform decision-making. Policymakers and regulators across Canada and internationally should prioritize risk-balanced policies, guidelines, and practice standards to support professional practice in the digital era.