Search Results (1,053)

Páramo ecosystems are among the most biodiverse and hydrologically critical landscapes on Earth, yet their long-term sustainability is increasingly threatened by climate-driven wildfires. Vegetation Cover Fires (VCFs) in these high-altitude environments degrade carbon stocks, disrupt freshwater regulation, and undermine biodiversity conservation goals central to the UN Sustainable Development Goals (SDGs 13, 15, and 6). Between 2001 and 2023, 128 fire events consumed approximately 815 ha in the Sumapaz locality (the world’s largest continuous páramo), representing 64.9% of all fires recorded across Bogotá’s 20 localities. Despite this disproportionate ecological and social impact, no spatially explicit, operational risk management framework has been available for the region, representing a critical sustainability governance gap. This study addresses that gap by proposing an integrated climate-adaptive risk assessment and management strategy based on (i) the Canadian Forest Fire Danger Rating System Fire Weather Index (FWI), derived from ERA5 reanalysis climate data; (ii) spatial and temporal hotspot analysis of MODIS FIRMS active fire detections; and (iii) IDEAM’s multi-component vulnerability and threat scoring protocol. Spatial data were processed using ArcGIS, and FWI sub-indices were computed for each month of the 2001–2023 period. The FWI averaged 0.78 (low danger) across the study period yet peaked at 13.7 in February 2010 (moderate-to-high danger), consistent with the year of highest recorded fire activity (19 events). High- and very high-risk areas (3.70% combined) coincide with slopes >25%, the presence of the invasive and pyrogenic Ulex europaeus, and proximity to populated and agricultural lands. This study concludes with a three-pillar risk management framework—risk knowledge, risk reduction, and disaster management—providing spatially targeted, operationally viable strategies for local and institutional actors that directly support the sustainable conservation of páramo ecosystem services (water supply, carbon sequestration, biodiversity). The framework is designed to be updatable on a monthly basis using freely available ERA5 data, enabling continuous adaptive governance of wildfire risk as a contribution to long-term territorial sustainability. Limitations regarding MODIS detection uncertainty, ERA5 spatial resolution in complex terrain, and the need for probabilistic modeling are explicitly acknowledged. Full article

Background/Objectives: X-linked hypophosphatemia (XLH), the most frequent heritable cause of hypophosphatemic rickets, is characterized by impaired linear growth and skeletal deformities, that can lead to disproportionate short stature. Linear growth depends on the coordinated regulation of systemic endocrine signals and local growth plate regulatory mechanisms controlling chondrocyte proliferation, differentiation, and apoptosis. This review critically discusses the molecular processes underlying growth impairment in XLH, with particular emphasis on growth plate dysfunction. Methods: A narrative review of experimental and clinical studies was conducted, focusing on growth plate biology, and on the pathophysiology of XLH. Particular attention was given to the role of systemic phosphate-regulating hormones, local paracrine factors, and intracellular signaling pathways, as well as the effects of current therapeutic strategies on linear growth. Results: Excess fibroblast growth factor 23 (FGF23) in XLH disrupts phosphate homeostasis and vitamin D metabolism, impairing skeletal mineralization and growth plate signaling. Beyond FGF23-related dysregulation, additional FGF23-independent mechanisms directly affect growth plate chondrocyte function and extracellular matrix composition, further contributing to growth plate disorganization. Current therapeutic approaches, including conventional phosphate and active vitamin D supplementation, FGF23 inhibition with human monoclonal antibody, and combination with recombinant human growth hormone, exert heterogeneous effects on linear growth through distinct biological mechanisms. Conclusions: Growth impairment in XLH reflects the combined impact of systemic endocrine dysregulation, and intrinsic growth plate dysfunctions. A better understanding of these mechanisms may facilitate the development of targeted therapeutic strategies, improving growth outcomes in individuals with XLH. Full article

Background/Objectives: Textbook outcome (TO) is an all-or-none composite in which a common, practice-sensitive component may exert disproportionate influence on patient classification. We evaluated the classification impact of binary postoperative intensive care unit (ICU) admission and the additional information retained by actual ICU duration after colorectal cancer surgery. Methods: This retrospective single-center cohort included 241 patients undergoing colorectal cancer resection between 2020 and 2026. Comprehensive TO required no major postoperative complication, reoperation, 30-day mortality, or postoperative ICU admission, together with microscopically margin-negative (R0) resection of the colorectal primary and postoperative length of stay ≤14 days. Core TO omitted ICU admission and length of stay and was used as an analytical comparator rather than as a newly validated TO definition. Patient-level reclassification was the primary outcome. ICU duration was evaluated continuously in the principal concurrent-association analysis; the 0-, 1-, 2-, and ≥3-day categories were exploratory. Results: Comprehensive and core TO were achieved in 27 (11.2%) and 169 (70.1%) patients, respectively, resulting in reclassification of 142 patients (58.9%; exact McNemar p < 0.001). ICU admission alone accounted for reclassification in 118 patients (49.0% of the cohort). Each additional ICU day showed a concurrent association with higher odds of core TO failure (adjusted odds ratio (OR), 1.43; 95% confidence interval (CI), 1.25–1.63) and major postoperative complications (adjusted OR, 1.63; 95% CI, 1.40–1.91; both p < 0.001). Categorical estimates for 1- and 2-day stays were imprecise and did not establish equivalence with no ICU admission. Duration-sensitive representations showed better internal model fit, discrimination, and probabilistic performance than binary ICU admission. Conclusions: In this center with frequent postoperative ICU utilization, binary ICU admission dominated comprehensive TO classification. ICU duration retained additional clinical information, but the findings do not establish the intrinsic invalidity of the ICU component, equivalence of short stays with no ICU admission, or a universal duration cutoff. Multicenter external validation across different ICU policies is required. Full article

Railway turnouts are subject to disproportionately high maintenance costs, partly driven by ballast void formation under asymmetrically loaded sleepers. Existing turnout models rely on detailed three-dimensional finite element track representations and do not readily support iterative long-term settlement analyses across the complete turnout geometry. This paper presents a computationally efficient physics-based vehicle–track interaction (VTI) framework extended to railway turnouts, incorporating a dual track model with equivalent foundation stiffnesses, a rail pad layer, and a crossing nose impact model. A modular sleeper dynamics model, formulated as an Euler–Bernoulli beam on a tensionless Winkler foundation, is coupled with the VTI framework to compute spatially resolved dynamic ballast pressure distributions along individual sleepers. A local pressure-based settlement model then allows the study of sleeper–ballast void formation over repeated axle passes. The framework is applied as a proof of concept to two in-service railway turnouts, one with and one without under sleeper pads, and complemented by a parametric study varying train speed, vehicle type, and rail pad stiffness. Void formation concentrates in the crossing nose region, consistent with laboratory measurements and particle-scale simulations. Under sleeper pads reduce peak ballast pressure by 38 to 44% and substantially reduce void formation across the crossing panel, thereby lowering overall track settlement and supporting the maintenance of track geometry in the turnout during operation. Vehicle type is the dominant influencing factor, with the locomotive producing up to 83% higher peak pressure than the passenger car model. The proposed framework provides an efficient tool for comparative turnout design, offering insight into the force transfer and settlement mechanisms of railway turnouts. Full article

Background/Objectives: B-cell acute lymphoblastic leukemia (B-ALL) remains the most common pediatric malignancy. This study aimed to evaluate clinical outcomes in pediatric B-ALL in Southern Mexico and determine how socioeconomic vulnerabilities—specifically indigenous status and treatment non-adherence—independently drive relapse and compromise survival in a resource-limited setting. Methods: A retrospective cohort study was conducted, including 146 patients (0–17 years) treated between 2010 and 2024 using modified Total XIII and XV protocols. Survival was estimated via Kaplan–Meier. Independent prognostic factors for overall survival (OS) and relapse were identified using multivariable Cox proportional hazards models. Results: The 5-year OS was 50%, and event-free survival (EFS) was 37.6%. Survival varied significantly by clinical risk: 88% for low-risk, 77% for standard-risk, and 31% for high-risk patients. Relapse occurred in 45.8% of patients. Beyond established biological predictors like hyperleukocytosis and high-risk cytogenetics, socioeconomic vulnerabilities profoundly impacted outcomes. Documented treatment non-adherence significantly reduced 5-year OS (23.4% vs. 56.1%, p = 0.001) and disproportionately affected indigenous patients (55.5% vs. 10.1% in non-indigenous). Multivariable analysis identified indigenous status as an independent predictor of increased relapse hazard (HR = 1.89, p = 0.049), alongside male sex and high leukocyte count. Conclusions: Survival outcomes in this cohort are markedly lower than in high-income countries. The high incidence of relapse is deeply intertwined with local structural inequities. Improving survival requires complementing biological risk stratification with targeted strategies to overcome socioeconomic barriers and prevent treatment non-adherence. Full article

Background: Italy exhibits a socioeconomic divide between its northern and southern regions, which extends into healthcare delivery and biomedical research. Medical oncology is particularly affected by this structural imbalance. This paper examines geographic disparities in clinical trial scientific publication output, citation impact, research funding, and collaboration networks in medical oncology between northern and southern Italy. Methods: A narrative bibliometric analysis was conducted using data from PubMed and other institutional databases of Italian Scientific Institutes for Hospitalization and Care. Data from the Italian National Agency for the Evaluation of Universities and Research Institutes, the Alliance Against Cancer, and the Italian Association for Cancer Research were also reviewed. Regional output was compared across two macro-areas, namely north and south Italy. Results: Northern Italian institutions account for a disproportionate share of publications, high-impact citations, and funded research projects. Northern Italy produces an estimated four to six times more medical oncology papers than southern Italy, driven by a higher concentration of cancer institutes, better-funded university hospitals, and stronger multidisciplinary infrastructure than in the south. Clinical trial density is highest in the north compared to the south (0.53 versus 0.02 per 100,000 inhabitants). Conclusions: The north–south divide in Italian oncology research productivity is real, multi-factorial, and persistent. The analysis reveals a substantial gap in research productivity, institutional capacity, and access to clinical trials between the two macro-regions. Targeted policy interventions, including decentralized trial models, dedicated funding streams for southern institutions, and stronger infrastructure for inter-regional collaboration, are urgently needed to ensure representativeness in oncology evidence generation and equitable scientific progress. Full article

The Nationality and Borders Act (NABA) 2022 changed the application of the standard of proof in asylum claims. Previously, the standard of proof applied to the whole claim was ‘to a reasonable degree of likelihood’. Following NABA for claims lodged on or after June 28 2022, the new standard applied utilises a two-pronged approach: The decision-maker must first decide on a ‘balance of probabilities’ whether the asylum seeker has a characteristic which could cause them to fear persecution for reasons of race, religion, nationality, membership of a particular social group or political opinion. Next, the decision-maker must determine whether ‘to a reasonable degree of likelihood’ that the claimant would be persecuted if returned to their country of nationality. The shift in the standard of proof reverts back to pre-Karanakaran where it had been decided that one standard should be used holistically. The two-pronged approach will inevitably cause the same confusions it did prior to Karanakaran as well as have a particularly disproportionate impact on people who are basing their asylum claims on their sexual orientation. This article investigates this disproportionate impact and argues that the shift in the standard of proof manufactures vulnerability and is a missed opportunity to rectify issues already existing with the standard of proof. Full article

Leucine-rich repeat kinase 2 (LRRK2) has emerged as a central molecular node linking genetic risk, membrane trafficking, lysosomal homeostasis, and immune signalling in Parkinson’s disease (PD). Rather than functioning as a conventional protein kinase, LRRK2 operates as a conformationally regulated, Rab-directed signalling machine whose activity is governed by long-range interdomain communication, membrane recruitment, and cooperative interactions with small GTPases. Converging advances in cryo-electron microscopy, quantitative phosphoproteomics, and human genetics indicate that pathogenic mutations, lysosomal stress, and pharmacological inhibitors do not simply alter catalytic output, but reshape the conformational landscape of LRRK2, biasing it toward distinct structural states with divergent cellular consequences. A defining feature of this system is the selective phosphorylation of Rab GTPases at low stoichiometry—most prominently Rab8 and Rab10—yet with disproportionate functional impact on vesicle trafficking, ciliogenesis, autophagy, and organelle positioning. The identification of Rab-directed phosphatases, particularly PPM1H, further establishes that LRRK2 signalling is governed by a dynamically balanced kinase–phosphatase circuit operating in space and time. These observations, together with emerging evidence linking LRRK2 activation to lysosomal damage and immune pathways, support a unifying hypothesis: PD-associated LRRK2 dysfunction arises from maladaptive stabilization of specific conformational and spatial states within a membrane-responsive signalling network, leading to persistent misregulation of Rab-dependent trafficking and organelle homeostasis, rather than from kinase hyperactivity alone. In this review, we integrate structural, biochemical, and cellular evidence to advance this framework and discuss its implications for disease mechanisms and therapy. We highlight key unresolved challenges—including conformation-selective drug targeting, spatial control of Rab phosphorylation, and context-dependent immune–neuronal crosstalk—and propose that restoring physiological regulation of LRRK2, rather than simply inhibiting its activity, will be essential for achieving mechanism-based disease modification in Parkinson’s disease. Full article

Modal shift in urban transportation is forecast to increase the frequency of tram interactions with Vulnerable Road Users (VRUs), who are disproportionately susceptible to injury. This report describes the outcomes of a research programme to identify the limitations of existing tram–VRU crash-compatibility guidelines. A targeted search of Scopus, Google Scholar and the grey literature resources yielded 27 results for inclusion in this study, covering three areas affecting tram–VRU collisions and interactions. These areas were: body regions susceptible to injury, speed and location of reported collisions, and VRU rider preferences around roads and tram infrastructures. This informed recommendations on future tram–VRU crash-compatibility guidelines. Injury criteria correlating to head, thorax and lower extremities should be considered, to enable up to ~78–84% of serious (AIS3+) injuries from real-world tram–pedestrian collisions to be captured in crash-compatibility studies. Although most tram–VRU collisions occur around stops or crossings, increasing vehicle impact speed in testing from 20 km/h to 30 km/h would enable most high-severity injuries from collision data to be captured. Based on VRU-stated or observed preferences, cyclists and e-scooter users should be considered travelling perpendicular to road infrastructures in tram–VRU collisions. Implementation of such recommendations into tram–VRU crash-compatibility guidance would account for a greater proportion of real-world interactions. Full article

Carbon pricing has emerged as a central policy tool for addressing climate change and advancing corporate environmental responsibility, yet its impact on firm-level investment and capital allocation remains insufficiently understood, particularly in emerging economies. This study examines whether emissions trading systems (ETS) influence corporate investment behavior and the reallocation of capital, using China as a representative case within the Asia-Pacific region. Employing a panel dataset of 5000 Chinese listed firms (approximately 80,000 firm-year observations) over the 2008–2023 period and a difference-in-differences framework, we identify the causal effect of carbon pricing on corporate investment decisions. The results show that firms exposed to carbon pricing experience a statistically significant reduction in investment following policy implementation. This effect is more pronounced in high-emission industries and operates through declines in profitability and tighter financial conditions. Asset-weighted measures indicate that the adjustment is concentrated among larger firms, and industry-level analysis shows that reductions are disproportionately driven by high-emission sectors. This pattern of heterogeneous investment responses is consistent with carbon pricing influencing investment allocation across firms; however, we do not directly observe the subsequent destination of capital or whether reduced investment in exposed firms is transferred toward cleaner activities. These findings provide new micro-level evidence that carbon markets shape corporate environmental management and real economic decisions by altering firm incentives, cost structures, and expectations. The study contributes to the literature by linking environmental policy tools to firm-level investment behavior and offers practical insights for policymakers and managers navigating the low-carbon transition in emerging economies. Full article

Coffee fermentation is a critical yet under-optimized stage of the coffee value chain, with significant implications for beverage quality, process consistency, and smallholder livelihoods. Pichia species, together with several non-Saccharomyces yeasts historically associated with the genus, are frequently detected in natural and semi-dry coffee fermentation; however, their functional roles remain insufficiently characterized, constraining evidence-based starter-culture design. Direct coffee evidence implicates P. kudriavzevii, P. kluyveri, and Meyerozyma guilliermondii (formerly Pichia guilliermondii) in substrate transformation, fermentation dynamics, and sensory quality development. However, these findings are derived exclusively from studies conducted on single farms during single harvest seasons, without independent validation across multiple farms, harvest seasons, origins, or production environments, limiting their broader applicability. In contrast, ecologically prevalent species, including P. fermentans, Wickerhamomyces anomalus (formerly Pichia anomala), and Debaryomyces hansenii (formerly Pichia hansenii), remain largely unexplored in the context of coffee fermentation. To contextualize the current knowledge and identify promising avenues for future research, this review synthesizes evidence from cocoa, Baijiu, bakery, vinegar, dairy, and other solid-state fermentation systems. Across these diverse matrices, Pichia and related non-Saccharomyces yeasts frequently exert a disproportionate influence on flavor development, microbial succession, and process stability relative to their population abundance. The reported mechanisms include ester and higher-alcohol production, modulation of bacterial community dynamics, extracellular enzymatic activity, and bioprotective effects. Notably, functional impact often occurs without numerical dominance; ester production can increase alongside declining ethanol yield, and ecological persistence may increase despite declining absolute abundance, implicating community-level interactions in addition to direct metabolic activity. However, both the mechanisms and the magnitudes of these effects vary across fermentation systems, underscoring that functions demonstrated in one matrix cannot be assumed to translate directly to coffee without experimental validation. Future progress will require strain-level characterization, mechanistic studies, deliberate multi-species consortium design, process optimization, and field-scale validation in diverse coffee-producing environments. Such efforts will provide a scientific foundation for evidence-based starter-culture development capable of improving coffee quality, consistency, and producer value. Full article

International shipping decarbonization has expanded beyond technical and operational regulation to include contested market-based bargaining. The proposed International Maritime Organization (IMO) Net-Zero Framework (NZF) combines a marine fuel standard with an economic compliance mechanism. Drawing on IMO submissions, voting records, official statements, and domestic and sectoral materials, this two-level game analysis examines why support sufficient to approve the draft for circulation in April 2025 did not translate into timely adoption later that year. The evidence suggests that the initial agreement space was not durable enough to support adoption on the planned timetable. At Level I, bargaining involved three linked dimensions: rule-making authority, responsibility allocation, and transition pathway design. At Level II, domestic, regional, and sectoral constraints included regulatory credibility and investment signals for the European Union; sovereignty and cost concerns for the United States; trade exposure and disproportionate impacts for trade-exposed emerging economies; ambition and revenue-supported transition for small island developing States; and fuel availability, fleet competitiveness, and legal certainty for energy exporters and open registries. A coalition sufficient at one procedural stage may therefore not remain sufficient at the next. A more durable agreement space would likely require an IMO-centered regulatory core, targeted enabling support, an ambition floor with compliance flexibility, and sequenced implementation and review. Full article

Background: Residential radon exposure is a leading risk factor for lung cancer, and climate change may exacerbate this risk by increasing radon entry into homes. In North Carolina (NC), disparities in lung cancer outcomes and low radon awareness disproportionately affect racially and ethnically diverse and low-income populations. However, little is known about how use of conventional address-based sampling (ABS) compares with community-engaged recruitment strategies for enrolling historically underrepresented populations into such research. Community-engaged approaches are used to improve participation in environmental health research, yet few studies compare their effectiveness with traditional approaches in NC. This manuscript compares recruitment outcomes between ABS and community-engaged approaches within the CLOVER study to address this gap. Materials and Methods: The Climate Impact on Lung Cancer via Exposure to Radon (CLOVER) study is a cross-sectional study examining climate-impacted radon exposure and lung cancer risk in NC. Participants were recruited using either ABS through a commercial address database or targeted community-engaged approaches implemented through partnerships with community organizations and culturally responsive, in-person outreach events. After providing informed consent, participants completed a household survey and a 7-day home radon test. Recruitment outcomes—consent, survey completion, and radon test return—were stratified by race and ethnicity and compared across strategies. Results: Of 236 consented participants, community-engaged recruitment enrolled a higher proportion of Non-Hispanic (NH) Black, Hispanic/Latino, and American Indian participants than ABS (57.3% vs. 41.9%). Community-engaged recruitment also had a higher consent rate than ABS (10.2% vs. 1.3%). Of the 145 participants who completed the survey, ABS participants completed surveys at a higher rate than community-engaged participants (73.3% vs. 54.7%), while of the 86 who returned the radon test kits, community-engaged participants did so at twice the rate of ABS participants (44.7% vs. 22.1%). Conclusions: Community-engaged recruitment enrolled a more racially and ethnically diverse sample and achieved higher consent and return rates than ABS, though ABS participants completed surveys at a higher rate. These findings highlight the importance of community partnerships and in-person recruitment strategies to improve participation of historically underrepresented populations in environmental health research and support equitable approaches to radon mitigation and lung cancer prevention. Full article

Background: Upper airway tract infections (UATIs) are among the most common infectious diseases worldwide, accounting for an estimated 12.8 billion episodes annually and more than 8 million disability-adjusted life years (DALYs). Despite their generally self-limiting nature, their cumulative clinical, socioeconomic, and public health burden remains substantial, particularly in children, older adults, and low- and middle-income countries (LMICs). Methods: We performed a structured narrative review of the peer-reviewed literature and reports from major international health organizations to summarize the current evidence on the epidemiology, etiology, clinical impact, socioeconomic burden, prevention strategies, and future challenges associated with UATIs. Particular attention was given to the influence of antimicrobial resistance, vaccination policies, and lessons learned from the COVID-19 pandemic. Results: UATIs remain one of the leading causes of healthcare utilization worldwide. Children experience the highest incidence, averaging 6–8 episodes annually, whereas vulnerable populations are at increased risk of complications and hospitalization. Marked geographical disparities persist, with LMICs experiencing a disproportionate burden due to limited healthcare access, lower vaccination coverage, and higher complication rates. Inappropriate antibiotic prescribing continues to accelerate antimicrobial resistance, while the COVID-19 pandemic profoundly altered the epidemiology of respiratory infections and demonstrated the effectiveness of non-pharmaceutical interventions. Advances in vaccination, antimicrobial stewardship, rapid diagnostics, and novel therapeutic strategies offer promising opportunities to reduce disease burden. Conclusions: Reducing the global burden of UATIs requires integrated public health strategies combining equitable vaccine access, effective antimicrobial stewardship, strengthened healthcare systems, and sustained surveillance. Lessons learned from the COVID-19 pandemic provide a unique opportunity to improve preparedness for future respiratory outbreaks while addressing persistent regional inequalities in prevention and care. Full article

Objective: Patient safety culture (PSC) is a critical determinant of healthcare quality. This study aimed to assess the current status of PSC among healthcare workers at Kien An Hospital, Hai Phong, Vietnam, and identify associated factors. Methods: A cross-sectional survey was conducted using the 12-dimension hospital survey on patient safety culture (HSOPSC). A total of 324 healthcare professionals (physicians, nurses, and allied staff) participated. Data were analyzed using descriptive statistics and multivariable logistic regression. Results: The positive response rate (PRR) across the 12 dimensions of patient safety culture (PSC) varied widely. The highest positive perceptions were observed in “Teamwork within units” (98.5%) and “Teamwork across units” (98.1%). Conversely, severe vulnerabilities in psychological safety were identified, with “Communication Openness” recording the absolute lowest PRR at 25.9%, closely followed by “Non-punitive response to error” at 29.0%. Comparative analysis between professional strata revealed broad alignment across 11 dimensions, with the sole significant divergence occurring in “Feedback and communication about error”, where physicians reported a significantly higher PRR than nurses & allied staff (85.8% vs. 75.2%; p = 0.04). In the multivariable logistic regression model, age emerged as the single independent predictor of overall positive PSC; compared to early-career staff (<30 years), healthcare workers aged 30–40 years (AOR = 4.17, p = 0.02) and 40–50 years (AOR = 5.03, p = 0.02) had significantly higher odds of favorable safety perceptions. Conclusions: Healthcare workers at the study hospital exhibit exceptionally strong collaborative teamwork, yet low communication openness and the fear of a punitive environment remain critical systemic barriers to safety. Because safety culture challenges are macro-institutional and disproportionately impact junior personnel, interventions should shift away from role-specific policies. Instead, hospital leadership must prioritize establishing non-punitive reporting mechanisms, enhancing open dialogue, and designing targeted safety culture onboarding initiatives tailored specifically to the needs of early-career healthcare workers to foster continuous organizational learning. Full article