Plateau icefields are large stores of fresh water, preconditioned to enhanced mass loss due to their gently sloping accumulation areas. Accurate modelling of their mass balance is therefore crucial for sea-level rise projections. Here, we use the COupled Snowpack and Ice surface energy and mass-balance model in PYthon (COSIPY) to simulate historical and future mass balance of the Juneau Icefield, Alaska – a high elevation (>1200 m) plateau icefield. We force the model with dynamically downscaled climate simulations, for both past and future (RCP 8.5) conditions. The icefield's mass balance decreased from a mean of −0.22 ± 0.38 m w.e. a−1 (1981–2019) to −1.52 ± 0.27 m w.e. a−1 (2031–2060), with many glaciers shifting from positive to negative mass balances at the start of the 21st century. This mass loss is attributed to projected rising air temperatures and reduced snowfall, causing the equilibrium line altitude to rise and triggering albedo and melt-elevation feedbacks. These processes exacerbate melt, potentially leading to increased glacier disconnections at icefalls.

Background: The molecular and epidemiological landscape of C. difficile infection (CDI) has evolved markedly in the last decade; however, limited information is available contrasting differences between adult and pediatric populations. We describe a multicenter study evaluating healthcare-associated (HA) and community-associated (CA) adult and pediatric-CDI identified in the Canadian Nosocomial Infection Surveillance Program (CNISP) network from 2015 to 2022. Methods: Hospitalized patients with CDI were identified from up to 84 hospitals between 2015–2022 using standardized case definitions. Cases were confirmed by PCR, cultured, and further characterized using ribotyping and E-test. We used two-tailed tests for significance (p≤0.05). Results: Of 30,817 cases reported, 29,245 were adult cases [HA-CDI (73.2%), CA-CDI (26.8%)] and 1,572 were pediatric cases [HA-CDI (77.7%), CA-CDI (22.3%)]. From 2015 to 2022, HA-CDI rates decreased 19.7% (p=0.007) and 29.4% (p=0.004) in adult and pediatric populations, respectively (Figure 1). CA-CDI rates remained relatively stable in the adult population (p=0.797), while decreasing 60.7% in the pediatric population (p=0.013). Median ages of adult and pediatric patients were 70 (interquartile range (IQR), 58–80) and seven (IQR, 3–13) years, respectively. Thirty-day all-cause mortality was significantly higher among adult vs. Pediatric CDI patients (11.0% vs 1.4%, p < 0.0001). No significant differences in other severe outcomes were found. Ribotyping and susceptibility data were available for 4,620 samples: 3,558 adult (77.0%) and 1,062 pediatric (23.0%). The predominant adult and pediatric ribotypes (RT) were 106 (12.2/16.2%), 027 (11.4/3.2%), and 014 (8.8/8.2%). Overall, RT027 prevalence significantly decreased from 17.9% in 2015 to 3.2% in 2022 (p=0.003), while RT106 increased from 8.5% to 14.4%. Resistance rates among adult and pediatric isolates were similar for all antimicrobials tested except moxifloxacin (16.2% vs. 6.2%, p < 0.0001, respectively). Adult moxifloxacin resistance decreased from 30% to 6.3% from 2015 to 2022 (p=0.006). Adults with moxifloxacin-resistant CDI were older (median: 74 vs. 69 years, p < 0.001) and had higher thirty-day all-cause mortality (13% vs. 9.8%, p=0.041) and recurrence (10% vs. 5.7%, p < 0.001) compared to those with moxifloxacin non-resistant CDI, while these trends were not observed in pediatric patients. Among RT027 strains, moxifloxacin resistance decreased from 91.0% in 2015 to 7.1% in 2022. There was one metronidazole-resistant pediatric sample in 2018 and no resistance to vancomycin or tigecycline in either population. Conclusion: We have found differences in the epidemiological and molecular characteristics of adult and pediatric CDI, with higher thirty-day all-cause mortality among adults. Overall, RT106 has replaced RT027 as the predominant ribotype with a concomitant decrease in fluoroquinolone resistance.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.

This study offers a definition of preemptive reform, applies the concept to Mexico in the 1970s, describes the reaction of one target group of the Mexican reform effort, and develops a preliminary explanatory model of reactions to preemptive reform. Because preemptive reform has been an important element in Mexican politics, it is especially appropriate to examine the concept as it applies to the Mexican case. However, preemptive reform has been attempted elsewhere and these results may interest others who would seek to understand the phenomenon in a variety of settings.

The ancient human footprints in valley-bottom sediments in Tularosa Valley, New Mexico, are fascinating and potentially important because they suggest interactions between Pleistocene megafauna as well as great antiquity. The dating of those footprints is crucial in interpretations of when humans first came to North America from Asia, but the ages have larger uncertainties than has been reported. Some of that uncertainty is related to the possibility of a radiocarbon reservoir in the water in which the dated propagules of Ruppia cirrhosa grew. As a test of that possibility, Ruppia specimens collected in 1947 from nearby Malpais Spring returned a radiocarbon age of ca. 7400 cal yr BP. We think it would be appropriate to devise and implement independent means for dating the footprints, thus lowering the uncertainty in the proposed age of the footprints and leading to a better understanding of when humans first arrived in the Americas.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

We link cleansing effects to contemporary cognitive theories via an account of event representation (intersecting object histories) that provides an explicit, neurally plausible mechanism for encoding objects (e.g., the self) and their associations (with other entities) across time. It explains separation as resulting from weakening associations between the self in the present and the self in the past.

Background: Healthcare services are increasingly shifting from inpatient to outpatient settings. Outpatient settings such as emergency departments (EDs), oncology clinics, dialysis clinics, and day surgery often involve invasive procedures with the risk of acquiring healthcare-associated infections (HAIs). As a leading cause of HAI, Clostridioides difficile infection (CDI) in outpatient settings has not been sufficiently described in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) aims to describe the epidemiology, molecular characterization, and antimicrobial susceptibility of outpatient CDI across Canada. Methods: Epidemiologic data were collected from patients diagnosed with CDI from a network of 47 adult and pediatric CNISP hospitals. Patients presenting to an outpatient setting such as the ED or outpatient clinics were considered as outpatient CDI. Cases were considered HAIs if the patient had had a healthcare intervention within the previous 4 weeks, and they were considered community-associated if there was no history of hospitalization within the previous 12 weeks. Clostridioides difficile isolates were submitted to the National Microbiology Laboratory for testing during an annual 2-month targeted surveillance period. National and regional rates of CDI were stratified by outpatient location. Results: Between January 1, 2015, and June 30, 2019, 2,691 cases of outpatient-CDI were reported, and 348 isolates were available for testing. Most cases (1,475 of 2,691, 54.8%) were identified in outpatient clinics, and 72.8% (1,960 of 2,691) were classified as community associated. CDI cases per 100,000 ED visits were highest in 2015, at 10.3, and decreased to 8.1 in 2018. Rates from outpatient clinics decreased from 3.5 in 2016 to 2.7 in 2018 (Fig. 1). Regionally, CDI rates in the ED declined in Central Canada and increased in the West after 2016. Rates in outpatient clinics were >2 times higher in the West compared to other regions. RT027 associated with NAP1 was most common among ED patients (26 of 195, 13.3%), whereas RT106 associated with NAP11 was predominant in outpatient clinics (22 of 189, 11.6%). Overall, 10.4% of isolates were resistant to moxifloxacin, 0.5% were resistant to rifampin, and 24.2% were resistant to clindamycin. No resistance was observed for metronidazole, vancomycin, or tigecycline. Compared to CNISP inpatient CDI data, outpatients with CDI were younger (51.8 ± 23.3 vs 64.2 ± 21.6; P < .001), included more females (56.4% vs 50.9%; P < .001), and were more often treated with metronidazole (63.0% vs 56.1%; P < .001). Conclusions: For the first time, CDI cases identified in outpatient settings were characterized in a Canadian context. Outpatient CDI rates are decreasing overall, but they vary by region. Predominant ribotypes vary based on outpatient location. Outpatients with CDI are younger and are more likely female than inpatients with CDI.

Funding: None

Disclosures: Susy Hota reports contract research for Finch Therapeutics.

Gilead et al.'s approach to human cognition places abstraction and prediction at the heart of “mental travel” under a “representational diversity” perspective that embraces foundational concepts in cognitive science. But, it gives insufficient credit to the possibility that the process of abstraction produces a gradient, and underestimates the importance of a highly influential domain in predictive cognition: language, and related, the emergence of experientially based structure through time.

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.