Research indicates that the giant sequoia, a serotinous conifer and the world's most massive tree species, is positively associated with high-severity fire for effective reproduction. However, land managers hypothesize that portions of giant sequoia groves could be lost in large crown fire areas due to a lack of regeneration, extensive montane chaparral cover, and long distances to the nearest surviving sequoia seed trees. Based on these hypotheses, rollbacks of environmental laws to facilitate intensive logging and tree plantation establishment are now proposed in giant sequoia groves on national forests and national parks, in the name of wildfire management and reforestation. Yet existing research is sparse, particularly regarding postfire sequoia regeneration that reaches the size of small trees (≥ 140 cm tall), which are most likely to survive to maturity. We investigated this issue in 62 field plots within the largest high-severity fire patches in Redwood Mountain Grove, Sequoia, and Kings Canyon National Parks, four years post-fire. These patches are dominated by crown fire but also include areas of high-intensity surface fire. At four years post-fire, we found sequoia regeneration density (mean = 19,478/ha) that was more than 21 times higher than initial modeling projected. Within the high-severity fire category, we found no correlation between fire severity or percent montane chaparral cover and giant sequoia small tree density, but found the percentage of all sequoia regeneration comprised by small trees is significantly higher in crown fire areas. The mean distance to the nearest live sequoia is now significantly shorter than reported at one year post-fire, suggesting that some live sequoias were not recognized as still living in initial evaluations. Our findings indicate that giant sequoia regeneration is thriving in large high-severity fire areas dominated by crown fire.
Anorexia nervosa (AN) is a severe psychiatric disorder (ED) with high mortality, marked functional impairment, and substantial phenotypical heterogeneity. Despite extensive research, treatment outcomes remain poor, and it is unclear why some individuals improve while others follow more persistent and severe courses. Existing diagnostic subtypes show limited value in predicting illness trajectory or treatment response. This study examined the distinct AN phenotypes which emerged within a treatment-seeking sample and considered how these differ in their response to standard treatment. Using data from the TRIANGLE study, latent profile analysis was used to identify phenotypic subgroups of adult patients with AN or atypical AN admitted to hospital for intensive care (n = 382), based on a variety of anthropometric and clinical variables. Following profile allocation, separate linear mixed model analyses (n = 370) examined differences between groups and over time (18 months) in depression, anxiety, and stress symptoms, work and social impairment, body mass index (BMI), and ED psychopathology. A four-profile solution best fit the data. Profiles differed in illness duration and symptom severity. One profile with long illness duration (mean ± standard deviation = 9 ± 7 years) and high symptom severity, a long-duration group (21 ± 11 years) with moderate severity, and two short-duration groups (4 ± 3 and 5 ± 3 years), one with high and one with comparatively lower severity, respectively. The high-severity, shorter-duration profile showed significant improvement across all variables over the 18-month follow-up period, whereas the highest-severity, longer-duration profile showed significant improvement on all variables except ED psychopathology. Where improvements were observed in both high-severity profiles, the magnitude of change was generally greater in the longer-duration profile, except for BMI, where it was equal and work and social impairment, where the shorter-duration profile showed greater improvement. In contrast, the lower-severity profiles showed significant improvements only in BMI and work and social impairment, which were smaller in magnitude than those observed in the high-severity profiles. Subtyping and treatment planning for AN must recognise that prognosis is shaped by multiple interacting factors rather than any single indicator and incorporate psychological, social, and functional complexity. Anorexia Nervosa (AN) is a complex mental disorder with heterogeneous symptom presentations. Recovery rates are suboptimal, and it is unclear which factors predict symptom remission in the shorter and longer term. The hypothesis that illness duration might contribute to explaining symptom severity has been proposed and has received some empirical support. However, it is becoming apparent that a more complex array of individual and clinical characteristics might better explain treatment response. In this study, we used a large dataset to examine the possibility of different, distinct presentations of AN. Using a data-driven approach, participants were grouped based on illness duration, body mass index, depression and anxiety symptoms, social and work functioning, autism traits, and eating disorder behaviours. Follow-up data were considered to examine the symptom trajectories of the different groups following standard treatment for AN. The results indicated the presence of four different groups in this dataset, defined by differences in symptom severity and illness duration. One group with long illness duration (9 years) and high severity, a very long-duration group (21 years) with moderate severity, and two shorter-duration groups with an average duration of 4 and 5 years, one with high and one with comparatively lower severity, respectively. The groups differed in their response to standard treatment; individuals with initially higher impairment showed the highest symptom improvement. The findings highlight that a single indicator, such as weight or length of illness, is not enough to subtype AN and predict prognosis. Treatment planning should consider different factors such as psychopathology, illness duration, and social impairments.
There are significant gaps in knowledge regarding the epidemiology, management, and outcomes of patients presenting to the emergency department (ED) with vaginal bleeding. This was a retrospective, successional cross-sectional study using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) examining all adult patients presenting to EDs with vaginal bleeding from 2011-2019. Patients were stratified by age, race/ethnicity, and pregnancy status. Main outcomes were ultimate outcome severity, presenting vital signs, and diagnostic tests performed. We defined high-severity outcome as any patient who was dead on arrival, died in the ED, or during that hospitalization; any patient admitted to the intensive care or stepdown units or to the cardiac catheterization lab or the operating room; or patients transferred to a non-psychiatric hospital. Moderate severity was defined as any patient admitted to floor-level care, held in observation, or transferred to a psychiatric hospital. We defined low-severity outcome as any patient discharged home. Patients presenting with a chief complaint of vaginal bleeding comprised 1.3% (95% CI, 1.2-1.4%,) of all ED visits, representing 14,620,933 total encounters. Of these patients, 53.0% (95% CI, 49.4-56.7%) were identified as pregnant. There was a lower prevalence of White patients presenting with this complaint compared to White patients presenting with any chief complaint (45.6% [95% CI, 41.9-49.4] vs 60.3% [95% CI, 57.7-62.8%]), with a reciprocal higher prevalence of Hispanic patients (21.1% [95% CI,17.7-24.5%] vs 13.2% [95% CI, 11.7-14.8%]). The majority of patients (88.1%, 95% CI, 86.1-90%) were classified as having a low-severity outcome, 10.3% (95% CI, 8.5-12.1%) were classified as moderate-severity, and 1.6% (95% CI,1.0-2.2%) as high-severity. Patients who were ultimately classified with high-severity outcomes had significantly higher shock indices at presentation and shorter wait times than patients with low-severity outcomes (0.75 [95% CI, 0.72-0.78] vs 0.68 [95% CI, 0.67-0.69], and 23.4 minutes [95% CI, 17.1-29.8] vs 41.7 minutes [95% CI, 37.1-46.4], respectively), despite no difference in median Emergency Severity Index triage score (2.5 [IQR 2.1-2.8] v 2.6 [IQR 2.2-2.9]). A quarter of patients (24.3% [95% CI, 20.8-27.7%]) received a pelvic exam: there were no significant differences in pelvic exam rate by age, pregnancy status, race/ethnicity, or ultimate outcome severity. Although most patients presenting to EDs with vaginal bleeding are discharged home, current triage models do not appear to appropriately risk-stratify higher risk patients. Disparities in presentation exist.
Background/Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) requires deep sedation, which is increasingly provided by anaesthetists using propofol-based regimens. However, real-world data on the incidence and predictors of anaesthesia-related adverse events (AEs) in this setting remain limited. The objective of this study was to assess the frequency, predictors, and clinical significance of adverse events during anaesthetist-delivered sedation for ERCP, based on a propofol regimen. Methods: We conducted a retrospective single-centre cohort study including 388 consecutive adult patients who underwent ERCP with propofol-based sedation administered by an anaesthetist. Adverse events were classified into three tiers: Tier 1 (any adverse physiological events, including haemodynamic and respiratory threshold crossings), Tier 2 (clinically significant events requiring pharmacological intervention-the primary regression outcome), and Tier 3 (high-severity outcomes, reported descriptively). Independent predictors of Tier 2 events were identified using multivariable logistic regression. Results: Adverse physiological events occurred in 220 patients (56.7%), the majority of which were minor and self-limiting. Clinically significant events requiring active pharmacological intervention occurred in 108 patients (27.8%), with vasopressor-treated hypotension as the predominant component (88 patients, 22.7%). All bradycardia episodes required atropine administration (34 patients, 8.8%), while desaturation was largely self-limiting, with advanced airway management required in only three patients (0.8%). High-severity outcomes were rare (9 patients, 2.3%). In multivariable logistic regression predicting clinically significant adverse events, propofol dose (OR 1.20 per 10 mg, 95% CI 1.14-1.25, p < 0.001), ASA physical status (OR 1.63, 95% CI 1.07-2.49, p = 0.024), age (OR 1.04 per year, 95% CI 1.01-1.07, p = 0.007), and ketamine use, confounded by indication (OR 2.18, 95% CI 1.14-4.14, p = 0.018) were independent predictors. Model fit was good (Nagelkerke R2 = 0.43). Conclusions: Adverse events are frequent when defined using inclusive criteria, but are predominantly minor in severity. Propofol dose is the principal modifiable risk factor, demonstrating a consistent dose-response relationship across multiple adverse outcomes. ASA physical status and age further identify patients at increased risk of clinically significant events requiring intervention. Ketamine use was associated with increased odds of adverse events; however, this association is likely confounded by indication and should not be interpreted as a direct causal effect. These findings support stepwise propofol titration guided by clinical sedation assessment, with avoidance of anticipatory dosing particularly in older patients and those with higher ASA scores, and highlight the safety of anaesthetist-led sedation in this setting.
In 1910, the U.S. federal government began an official policy of suppressing wildfires. Decades later it became understood that the giant sequoia, the world's most massive tree, is serotinous and depends upon fire to effectively reproduce. For a century, fire was almost completely excluded from giant sequoia groves, until a series of lightning fires over the past decade. After these fires, U.S. land managers hypothesized that the blazes had caused unprecedented levels of high-severity fire due to a century of fire suppression and fuel accumulation. Based on this assumption, U.S. legislation is now proposed to override environmental laws to allow logging in all giant sequoia groves on federal public lands, including in Wilderness Areas and national parks, in the name of wildfire prevention. In addition, lower-severity prescribed fires are now being implemented as a means to prevent and suppress mixed-severity wildfires, based on the assumption that high initial post-burn sequoia seedling densities after prescribed fire will translate to relatively high densities in later years. I investigated the effects of wildfire suppression in giant sequoia groves using GIS data of wildfire perimeters dating back to 1910, fire severity data from 2012 to present, and a government prescribed fire and sequoia regeneration dataset. I found fire of all severities since 1910 is below frequencies that occurred before fire suppression. I found no correlation between time-since-fire and the percentage of area burned comprised by high-severity fire in giant sequoia groves. Further, I found no correlation between initial (1 year post-burn) sequoia seedling densities and densities at 10 years following prescribed fire. The percentage of all plots lacking any sequoia regeneration after prescribed fire increased significantly over time. Only 23% of prescribed fire plots lacked sequoia regeneration at 1 year post-burn, while 82% of prescribed fire plots lacked sequoia regeneration at 20 years post-burn.
Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear. We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity. Unsupervised clustering of plasma cytokines identified three immunologic subgroups, including a high-severity group ("Group C") characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a strong association between hyperinflammatory cytokine signaling and lymphocyte dysfunction. Single-cell RNA sequencing revealed transcriptional signatures of T cell activation and metabolic stress, with suppression of a lymphoid protective gene program across CD8⁺ T cell subsets. Despite increased expression of activation markers, T cell receptor repertoire analysis revealed no dominant clonotypes, consistent with bystander activation. Phosphoflow cytometry demonstrated baseline STAT1/STAT3 hyperactivation in Group C CD8⁺ T cells, which failed to respond to αCD3/αCD28/αCD49d stimulation. These findings define an IL‑6/IFN‑γ-driven endotype of T cell dysfunction in pediatric sepsis and highlight the JAK/STAT axis as a rational target for immunomodulatory therapy. K12HD047349, K23GM159013, K08AI135091, R01HD095976, Thrasher Research Foundation, Burroughs Wellcome Fund CAMS, Immune Deficiency Foundation, Primary Immune Deficiency Treatment Consortium, Barbara Brodsky Foundation, CHOP Research Institute.
The efficacy of nitrogenous additives in deconstructing the lignin macromolecule is conventionally attributed to physical interactions. However, this macroscopic adsorption-centric model frequently overlooks the kinetic contributions of chemical lability at the molecular level. Here, we introduce a mechanistic decoupling strategy using melamine as an inert structural probe to benchmark against hydrolytically labile urea and dicyandiamide. We report an affinity-efficiency inversion: Urea, despite having the weakest theoretical binding energy, achieves the highest bulk delignification (~95%), surpassing the apparent physical ceiling (~85%) constrained by non-covalent interactions. This chemical override is driven by in situ generated nucleophiles acting as chemical etchants, amplified by localized structural relaxation to induce extensive depolymerization. Conversely, the inert melamine system operates via a distinct surface masking pathway. Rather than a kinetic limitation, the observed physical limit represents a thermodynamic complexation ceiling, where melamine leverages its superior affinity to form stable supramolecular complexes that passivate residual lignin. Mass balance analysis reveals a functional equivalence: surface passivation compensates for lower bulk purity, enabling the masking pathway to match the enzymatic glucose recovery of the high-severity erosion pathway. Our findings shift design principles for nitrogenous additives from maximizing solubility to tailoring specific erosion or masking functionalities, offering divergent structural engineering routes for highly monodisperse lignin nanospheres or functionalized supramolecular biocomposites.
Increasing demand for mental health care in Europe highlights the urgent need to improve access for high-risk patients. Smart screening tools may help identify patients at the highest risk for suicide, thereby reducing waiting times and decreasing mental health-related emergency visits. This study assesses the impact of a smart screening tool on identifying high-risk patients and reducing unplanned healthcare use. We conducted a retrospective, multicenter cohort study including 14,395 patients between January 1, 2022, and October 31, 2024, at four outpatient clinics in Madrid, Spain. Participants completed a validated symptom severity survey via a mobile application integrated into the electronic health record. An algorithm categorized patients based on symptom severity, prioritizing those with the highest severity for rapid outpatient evaluation (< 1 week). High-severity patients exhibited greater overall healthcare use (IRR 3.22; CI 3.15–3.29; p < 0.001) and unplanned healthcare use (IRR 1.99; CI 1.70–2.34; p < 0.001) during the year after referral. Male sex and younger age were associated with increased unplanned healthcare use. Among 7,070 patients classified as “highest risk”, 6,104 (86.3%) were prioritized for early outpatient care. Early evaluation significantly reduced emergency department visits among highest-severity patients (IRR 0.59; CI 0.51–0.69; p < 0.001) during the year after referral. This study aligns with the European health agenda advocating for digital transformation in mental healthcare. By facilitating early identification and intervention, smart screening tools can help reduce reliance on emergency care, optimize resource allocation, and promote equitable access to mental health services.
Late-onset neonatal sepsis (LOS) requires early recognition to reduce mortality and morbidity, but clinical signs are often nonspecific. We introduced a nurse-driven red-flag-based sepsis bundle in our Level IV NICU in 2021. We assessed its performance in detecting culture-positive LOS by stratifying the severity of illness. This retrospective observational study included infants 3 days and older who were evaluated for sepsis. Cases were stratified into Green (lowest severity), Amber, Yellow, or Red (highest severity) categories according to clinical and laboratory criteria. We assessed bundle performance by calculating sensitivity, specificity, predictive values, and the area under the receiver operating characteristic curve (AUROC) relative to the Green reference group. Of the 142 evaluated sepsis episodes, the bundle was used in 123 (86.6%). Sensitivity was robust across the severity groups: 85.1% for Amber, 73.7% for Yellow, and 90.0% for Red. However, the specificity was uniformly poor at 13.0%, and the AUROC values remained <0.52 across all categories. Although the bundle consistently identified high-severity cases, it frequently over-identified low-risk infants. The nurse-driven sepsis bundle demonstrated high sensitivity for severe LOS, ensuring no critical cases were missed, but lacked discriminative ability due to poor specificity. Integrating additional objective markers and validated diagnostic tools may enhance the specificity and clinical utility of LOS evaluations while supporting nursing autonomy in sepsis recognition. A video abstract summarizing this study is available as supplemental digital content.
Risk management is an essential aspect to patient safety, nevertheless many hospitals burden with delayed reporting, limited data accessibility, and insufficient analytical tools. Kalasin Hospital reported 37.3% unresolved incidents and an average reporting delay of 4.52 hours for high-severity risks (G/H/I). This study employed an innovative dashboard technology as real-time operative system; RTOS to enhance efficiency and timeliness in risk management. the research aimed to develop a dashboard technology system as RTOS for hospital risk management Methodology: Research and development (R&D) method was involved 50 purposively selected participants (Executives, Risk officers, Medical staff). Tools included interviews, focus groups, needs assessments, the developed dashboard (built on Google Data Studio with LINE Notify integration), and evaluation questionnaires. Data were analyzed using content analysis, descriptive statistics, and paired t-tests at p-value < 0.05. This research founded the developed dashboard system (using Google Data Studio connected to the Ponglang NRLS database and the LINE Notify alert system), And post-implementation, mean reporting time for G/H/I risks decreased from 4.52 to 1.18 hours (73.33%), on-time reporting rose from 35.20% to 87.50%, and data access time dropped from 12.8 to 2.3 minutes (82.03%). User satisfaction increased from 2.85 to 4.32 (51.58%). Applying the R&D with ADDIE model enabled the creation of a user centered RTOS dashboard that improved timeliness, data accessibility, and risk response. Expand dashboard use to other hospitals, standardize automated alerts, integrate AI for predictive analytics, and implement structured change management and training programs.
In Chile, wildfires caused mainly by human activity have led to substantial changes in forest composition and structure. These disturbances may promote irreversible forest degradation, particularly when critically endangered forests are affected by high intensity fires and invasion of exotic species. Understanding post-fire regeneration dynamics in endangered Nothofagus alessandrii forests, and the invasion of Pinus radiata under varying fire severities, is crucial to ensure the persistence of these ecosystems. This study examined the early post-fire response of N. alessandrii forest fragments embedded within a P. radiata plantation matrix following the 2017 'Las Máquinas' megafire in central Chile. Fire severity was assessed using the differenced Normalized Burn Ratio (dNBR) derived from Sentinel-2 imagery. Post-fire vegetation dynamics were analyzed using time series of two spectral indices (NDVI and MSAVI2) from 2018 to 2021, applying linear mixed-effects models based on PlanetScope imagery. Early post-fire responses of N. alessandrii forests and P. radiata invasion were evaluated through establishment density and tree-ring radial growth across different fire severity classes. Results showed rapid vegetation recovery in areas affected by moderate and high fire severity. Post-fire regeneration of N. alessandrii occurred mainly through vegetative resprouting, with higher resprouting rates observed in moderately and severely burned sites (70%) compared to low-severity areas (48%). Radial growth of N. alessandrii did not differ significantly between moderate and high severity sites (p > 0.05), while P. radiata showed increased growth under high fire severity and greater growth than native species in areas severely burned (p <0.05). A direct relationship was observed between fire severity and the degree of invasion by P. radiata, with high-severity sites showing the highest levels of invasion (9,760 ind/ha). These results highlight the increased vulnerability of this already endangered ecosystem to severe fires and the invasion of P. radiata. Both processes induce irreversible forest degradation by reinforcing a positive fire feedback loop and intensifying competition with native species in severely burned areas. These results indicate the urgent need to effectively control the P. radiata invasion in the burned forests of N. alessandrii to avoid the loss of the last remaining fragments of this threatened species.
This study aimed to estimate in-hospital mortality and identify prognostic factors in infective endocarditis (IE) in a Colombian multicenter cohort. This was a retrospective cohort study of 308 consecutive patients with definitive IE (modified Duke criteria) across four Colombian hospitals (2007-2017). Multivariate logistic regression identified independent mortality predictors. The primary outcome was in-hospital death. In-hospital mortality was 32.7% (101 of 308), with substantial across-center heterogeneity (9.6-45.9%), contrasting with European (EURO-ENDO 17.1%) and Latin American (25.1%) registries. Independent predictors of death in multivariable logistic regression were renal replacement therapy (adjusted odds ratio [aOR] 9.19, 95% confidence interval [CI] 4.61-18.34), perivalvular abscess (aOR 6.42, 95% CI 2.69-15.35), central nervous system embolism (aOR 3.07, 95% CI 1.63-5.80), older age (aOR 1.03 per year, 95% CI 1.01-1.05), and Staphylococcus aureus etiology (aOR 1.87, 95% CI 0.99-3.51). Surgery was independently protective (aOR 0.34, 95% CI 0.18-0.63), an estimate that persisted after propensity score adjustment. Of 199 patients with surgical indication, 78.9% underwent surgery; non-operated cases had prohibitive risk profiles. Model discrimination was good (area under receiver operating characteristic curve 0.842, 95% CI 0.791-0.894). Renal replacement therapy and perivalvular abscess are the strongest independent predictors of in-hospital mortality in this Colombian multicenter IE cohort, whereas cardiac surgery is protective but frequently precluded by prohibitive risk profiles. The 32.7% mortality reflects the high-severity spectrum of a tertiary referral population and is not generalizable to lower-complexity settings. Early identification of patients at risk for dialysis-requiring acute kidney injury and timely multidisciplinary surgical evaluation represent priority clinical intervention targets. In this Colombian multicenter cohort, in-hospital mortality was 32.7%, with substantial across-center heterogeneity. Renal replacement therapy and perivalvular abscess emerged as the strongest independent mortality predictors, identifying patients with limited physiological reserve and advanced infection. Surgery was strongly and consistently protective, including after propensity score adjustment, although unmeasured confounding by indication cannot be fully excluded. Whether multidisciplinary endocarditis team implementation can translate this prognostic information into mortality reduction in Colombian tertiary settings is a hypothesis that should be tested prospectively.
As climate change drives more frequent and intense wildfires, the revitalization of Indigenous fire stewardship grows increasingly urgent. This paper examines the Karuk Tribe's experiences with settler colonialism and their efforts to restore cultural fire stewardship in the wake of the 2020 Slater Fire, which burned 157,000 acres of Karuk ancestral territory. Through a collaborative, community-engaged case study approach, we conducted 13 interviews with Karuk Tribal members and staff to identify post-fire recovery priorities, explore management options, and examine governance systems affecting Karuk homelands. Participants emphasized that the criminalization of their traditional fire stewardship practices, now compounded by federal land management practices and ongoing obstacles to restoring their ecocultural stewardship, has resulted in forested landscapes prone to high-severity fire, posing a threat to their safety and well-being. Findings highlight how the oppressive forces of settler colonialism persist today, as Karuk people continue to experience barriers to enacting stewardship, sovereignty, and religious freedom. Participants described fire as essential for cultural continuity, ecosystem health, and Karuk governance. The Karuk Tribe's leadership-through policy advocacy, research partnerships, programs like Indigenous Women-in-Fire Training Exchange (TREX), and partnerships grounded in Indigenous data sovereignty-offers a model for advancing ecocultural stewardship. Post-fire landscapes present critical opportunities to reestablish Tribal stewardship and shift to more beneficial fire management paradigms. This research affirms that supporting Indigenous fire knowledge and practice is essential for effective place-based climate adaptation.
Large-scale outbreaks of infectious diseases, often spread through person-to-person contact, have historically caused significant morbidity and mortality. In this study, we develop a two-layer SIR (Susceptible-Infected-Recovered) model that accounts for individual mobility within and between populations. We explore two complementary approaches to disease mitigation: (i) an optimal control framework and (ii) an evolutionary behavior model. The optimal control approach minimizes the disease burden by coordinating three controls: travel restrictions, social distancing, and antiviral treatment, guided by predefined cost functions. In contrast, the behavioral model captures adaptive individual responses based on infection prevalence, interpopulation infection disparities, and socioeconomic trade-offs, following evolutionary game theory. We find that for high-severity epidemics, combining travel restrictions with social distancing significantly reduces infection peaks and total cases, while these measures become less effective for lower-severity outbreaks. Across all scenarios, a combined control strategy is most effective. However, a key finding is that antiviral treatment alone can rival the effectiveness of combined travel and distancing measures, offering a streamlined alternative when the societal costs of nonpharmaceutical interventions are prohibitive. Furthermore, optimally coordinated policies consistently outperform adaptive behavioral responses, yielding a significant reduction in the population.
Accurate valuation of flood risk is fundamental to efficient resource allocation, insurance pricing, and public investment in agriculture. Standard economic models, which often link asset damage directly to hazard magnitude, fail to capture the unique vulnerability of agricultural capital-where the value of standing crops is contingent upon phenological stage. This study develops a capital valuation framework to deconstruct the economic burden of flooding on cropland, demonstrating that the timing of a flood is a primary determinant of financial loss, often outweighing the role of physical flood magnitude. We model agricultural flood risk as expected annual damage (EAD) to crop capital, integrating hydrologic frequency analysis for a U.S. Midwest County with a phenologically-explicit damage function. This function disaggregates risk into two components: a Flood Hazard Index (FHI), quantifying flood intensity and duration across return periods, and a Flood Susceptibility Index (FSI), representing the time-sensitive depreciation rate of crop capital at different growth stages. Probability-weighted losses are summed across all flood scenarios to derive total EAD. Results reveal that the distribution of losses is heavily skewed toward high-probability, low-severity events. The 2-year and 25-year floods collectively account for approximately 45% of total EAD, despite extreme (≥ 100-year) events generating substantially larger per-event losses. Frequent floods impose the highest economic cost not because of peak discharge, but because their high likelihood of coinciding with phenologically sensitive periods is compounded by longer inundation durations-a "double liability" where occurrence probability and capital impairment duration are simultaneously maximized. Conversely, low-probability, high-severity events tend to occur outside the growing season, leaving lower-value capital exposed. These findings invert conventional risk models and carry significant implications for crop insurance design, flood mitigation investment, and agricultural capital management under climate volatility. The online version contains supplementary material available at 10.1007/s11269-026-04801-1.
Large language models (LLMs) offer opportunities for sexual health education, but integrating them into digital products presents clinical challenges and risks, particularly regarding clinical safety and monitoring at scale. This study designed and evaluated a safety-focused framework for an LLM-based sexual well-being chatbot in a mobile application. We conducted a methods-focused feasibility study comprising a multi-stage development and evaluation of the chatbot. We used an interdisciplinary, medically led three-phase development process, including a five-stage evaluation framework combining synthetic test cases, clinician-led vulnerability testing and controlled release to real users to assess clinical accuracy and safety. The chatbot met predefined precision and recall thresholds in synthetic testing. Clinically inaccurate responses remained below 2% across clinician review stages, with no high-severity unsafe responses. In a controlled release, 5195 real user interactions were reviewed. Clinically inaccurate responses occurred in 0.90% (47/5195) of dialogues, with unsafe responses within severity thresholds. This study demonstrates the feasibility of a structured framework for developing and evaluating LLM-based sexual health chatbots with clinical safety oversight. This approach helps to address gaps in safety reporting and could be adapted for other sensitive clinical domains.
Wildfire activity is increasingly characterized by larger fire events and a greater prevalence of high-severity burns, driven by climate change, land-use change, and prolonged fire suppression. These shifts are altering post-fire vegetation dynamics, yet uncertainty remains regarding how early post-fire plant responses vary with burn severity and pre-fire occurrence of invasive plants under contemporary fire conditions. Given limited capacity for post-fire monitoring and restoration across increasingly large fire-affected landscapes, identifying factors associated with early post-fire vegetation responses is critical for prioritizing surveillance and supporting invasive plant management through early detection and rapid response (EDRR) programs. The 46,000 ha McKay Creek Wildfire in interior British Columbia, Canada, provided an opportunity to examine how burn severity, topography, and pre-fire occurrence of invasive plants (based on mapped infestation extent) influence early post-fire vegetation composition across diverse ecosystems. We predicted that both high burn severity and pre-fire occurrence of invasive plants would be associated with increased non-native plant cover following wildfire. Vegetation cover was recorded by species and grouped by native status (native or non-native), and life cycle (annual, biennial, perennial), on 80 plots stratified by burn severity and pre-fire occurrence of invasive plants. Two years post-fire, vegetation cover was dominated by bare ground across all plots, while native plant cover exceeded non-native cover under all conditions. At the broad status-group level (native vs. non-native), post-fire vegetation cover did not differ meaningfully across burn severity classes or between areas with and without documented pre-fire occurrence of invasive plants. Instead, elevation was the strongest driver of early post-fire vegetation patterns, with native cover increasing and non-native cover and bare ground decreasing at higher elevations. When vegetation was disaggregated by status and life cycle, non-native annual cover was higher in high-severity burns and at lower elevations, and non-native perennial cover increased with elevation. At a time when wildfires are increasing in size, frequency, and intensity, and resources for recovery are limited, this study provides region-specific insights to support prioritization of early post-fire restoration activities such as monitoring, prevention and management of invasive plants, and planting of native species. La actividad de los fuegos de vegetación se está caracterizando por eventos de incendio cada vez más grandes y una mayor prevalencia de quemas de alta severidad, conducidas por el cambio climático, cambios en el uso de la tierra, y una prolongada era de supresión de fuegos. Estos cambios están alterando la dinámica de la vegetación en el post-fuego, y aún así, la incertidumbre permanece sobre cómo las respuestas de las plantas en el post fuego temprano varían con la severidad de la quema y con la ocurrencia de plantas invasoras en el período previo al fuego en las actuales condiciones de los incendios. Dada la limitada capacidad para monitorear en el post fuego y en la restauración a través de grandes paisajes afectados por fuegos, la identificación de factores asociados con la respuesta inicial de las plantas en el post fuego temprano es crítico para priorizar la vigilancia y el soporte del manejo de plantas invasoras a través de programas de rápida detección y respuesta rápida (EDRR). Las 46 mil ha del incendio de McKay Creek en el interior de la Columbia Británica, proveen de una oportunidad para examinar cómo la severidad de ese incendio, la topografía del lugar, y la existencia, previa al fuego, de especies invasoras (basados en mapas de extensión de la infestación), influencian la composición de la vegetación en el post fuego temprano y a través de diversos ecosistemas. Nuestra predicción fue que tanto la severidad de las quemas y la pre-ocurrencia de plantas invasoras, podría asociarse con un incremento en la cobertura de plantas invasoras (no nativas) en el post fuego temprano. La cobertura de la vegetación fue registrada por especies y agrupadas por su estatus (Nativas y No-nativas) y ciclo de vida (anuales, bienales, y perennes), en 80 parcelas estratificadas por la severidad del fuego y la existencia previa de plantas invasoras. Dos años luego del incendio, la cobertura vegetal fue dominada por el suelo desnudo en todas las parcelas, mientras que la cobertura de plantas nativas excedió a la de no-nativas bajo todas las condiciones. A nivel de estatus amplio (entre grupos de nativas vs. no-nativas) la cobertura post fuego no difirió significativamente entre las clases de severidad o entre áreas documentadas previamente con existencias o no de especies invasoras. En cambio, la elevación del terreno fue el factor conducente más importante de los patrones de vegetación encontrados en el post fuego, con una cobertura creciente de plantas nativas y un decrecimiento tanto de plantas no nativas como de suelo desnudo a mayores elevaciones. Cuando la vegetación fue desagregada por estatus y ciclos de vida, la cobertura de anuales no-nativas fue mayor en quemas de alta severidad y a bajas elevaciones, y la cobertura de plantas perennes no-nativas se incrementó con la elevación. Cuando los incendios de vegetación se incrementan en tamaño, frecuencia, e intensidad, y los recursos para la recuperación de la vegetación son limitados, este estudio provee de percepciones específicas de valor regional para priorizar actividades de restauración post fuego como el monitoreo, prevención, y manejo de plantas invasoras, y la plantación de especies nativas.
Newer methicillin-resistant antimicrobials are needed to address the rising prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative (MRCONS) infections. We describe two contrasting, recalcitrant staphylococcal infections successfully managed using early transition to the oral benzoquinolizine antibiotic alalevonadifloxacin, highlighting its utility in complex clinical settings. Two high-severity cases of staphylococcal infections are presented. Patient 1, a 58-year-old metastatic lung and orthopedic implant infection on hemodialysis, developed catheter-associated MRSA sepsis with bacteremia, endocarditis, and metastatic lung and orthopedic implant infection. Patient 2, a 41-year-old male with a prior craniotomy, presented with a chronic cranial wound infection due to methicillin-resistant Staphylococcus hominis (MRCONS) originating from an infected ex vivo bone flap. Both patients initially received intravenous therapy and were transitioned to oral alalevonadifloxacin upon availability of susceptibility data. Levonadifloxacin susceptibility testing showed an MIC of 2 µg/mL for MRSA and 0.047 µg/mL for MRCONS-SCV. Patient 1 received 7 weeks of oral therapy aligned with POET recommendation for endocarditis, while Patient 2 completed 8 weeks of oral therapy consistent with OVIVA-based management of osteomyelitis. Despite significant challenges, both patients demonstrated rapid clinical improvement, resolution of infection, and no relapse during follow-up. These cases support oral alalevonadifloxacin as an effective and safe step-down option for complex MRSA and MRCONS infections, including endocarditis, osteomyelitis and meningitis. Alalevonadifloxacin (prodrug of levonadifloxacin) offers a promising oral treatment option when conventional agents are not suitable.
To identify molecular biomarkers associated with chronic liver failure (CLF) progression to acute-on-chronic liver failure (ACLF). RNA-seq data from 8 CLF patients-stratified into high-severity (G, ACLF with total bilirubin ≥171 μmol/L) and low-severity (L, stable CLF with total bilirubin <171 μmol/L) groups-along with 4 healthy controls were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-associated gene modules. A total of 3112 differentially expressed genes (DEGs) were identified, with KEGG analysis showing enrichment in innate immune pathways. Metabolomic profiling revealed 63 differentially expressed metabolites (DEMs), with four bile acids-Glycochenodeoxycholic acid, Glycocholic acid, Glycodeoxycholic acid, and Lithocholic acid-identified as key metabolites in bile acid biosynthesis pathways. Strong negative correlations were observed between these hydrophobic bile acids and 33 hub genes. Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts.