Monitoring air quality is crucial for understanding and improving public health. There is interest in developing ultra-sensitive, low-power, cost-effective sensors. This work demonstrates that structural modulation of Sn nanoparticles through controlled deposition and oxidation enables a transition from metallic to semiconducting percolative networks, significantly enhancing NO2 sensing performance at room temperature. The proposed percolation-driven sensing mechanism provides a new framework for understanding charge transport and gas interaction in nanostructured metal oxide systems. The nanoparticles are deposited near the percolation threshold for electrical conduction and, upon exposure to air, consist of a tin core and an amorphous Sn3O4 surface. Post-deposition heating in air at 320 °C for two hours forms SnO and Sn3O4 on top of the gold electrodes and polycrystalline SnO in the tetragonal litharge phase, known as Romarchite, on the glass between the electrodes. Both as-deposited and heat-treated sensors were capable of detecting NO2 at room temperature, with a limit of detection in the parts-per-billion range. A percolation model is used to explain their operating currents, in which NO2 reacts at nanoparticle gaps and intra-grain boundaries to form charge-depletion regions that primarily determine their resistance. Heat treatment has also been found to cause disproportionation of SnO, resulting in tin-rich precipitates and increasing the operating current to the milliampere range. These precipitates, although oxidized on their surfaces when exposed to air, may serve as bridges that reduce the total resistance of the percolating paths.
PurposeTo examine the relationship between fall-related mortality, disability-adjusted life years (DALY), healthcare expenditures, and research funding and determine whether fall prevention funding is proportional to fall-related public health impact.DesignCross-sectional.SettingUnited States.SampleNot applicable.MeasuresMortality rates (2018-2022) for leading causes of death were obtained from CDC WONDER. Disability-adjusted life-year (DALY) rates (2021) were obtained from the World Health Organization. Healthcare expenditures (2016) were obtained from the Institute for Health Metrics and Evaluation. Research funding data (2018-2022) were obtained from NIH ExPORTER and linked to causes of death using MeSH term searches.AnalysisLinear regression models were used with log-transformed research funding as the dependent variable and log-transformed mortality rates, DALY rates, and healthcare expenditures as predictors.ResultsFall mortality rate was 13.1 deaths per 100 000 individuals, fall-related DALY rate was 713.2 per 100 000, and fall-related healthcare expenditures were $106.6 billion. Falls ranked 12th in mortality, 8th in DALY, and 5th in healthcare costs but 20th in research funding, receiving $489 million over 5 years. Falls received significantly less funding than expected based on mortality rates (predicted $1.95 billion), DALY rates (predicted $3.27 billion) and healthcare expenditures (predicted $5.63 billion).ConclusionAlthough falls have a significant impact on older adults' health and mortality, fall research funding is disproportionately low. To reduce mortality and mitigate rising healthcare costs associated with falls, federal investment in fall prevention research should be a higher priority.
To estimate the global, regional and national economic impact of periodontitis in 2021 (including expenditure on prevention, diagnosis, treatment, maintenance and rehabilitation), and to forecast expenditures through 2050 under two utilisation scenarios: continuation of current treatment coverage trends and an illustrative expanded coverage scenario. A cohort-based gross-costing Monte Carlo model was developed to estimate global, regional and national expenditure on periodontitis in 2021. Model estimates were validated against known national periodontal spending and aggregate dental expenditure. The model was then applied to generate forecasts for 2025-2050 at five-year intervals under two utilisation scenarios: (i) continuation of current utilisation patterns of periodontal care and (ii) an illustrative expanded coverage scenario in which 80% of the population receives periodontal care by 2030. In 2021, global expenditure on periodontitis was US$168.1 billion (95% UI: 133.8-202.4), with marked regional disparities; five countries (the United States, China, Germany, Japan and France) accounted for more than two-thirds of global spending. Under current utilisation trends, global expenditure is projected to increase modestly to US$174.9 billion by 2050 (95% UI: 137.4-212.3), despite a projected 44.3% increase in severe periodontitis prevalence. Under the expanded coverage scenario, expenditure would instead increase threefold to US$500.6 billion (95% UI: 389.2-612.1) by 2050, implying an annual financing gap of US$325.7 billion. Global per-capita expenditure was US$21.32 (95% UI: 16.97-25.67) in 2021, projected to decline to US$18.36 (95% UI: 14.43-22.29) in 2050 under current utilisation, but to rise to US$52.56 (95% UI: 40.86-64.26) under the expanded coverage scenario. Periodontitis imposes a substantial and unequally distributed economic impact worldwide. Under current utilisation patterns, the projected rise in prevalence by 2050 will primarily translate into unmet care needs. Achieving universal coverage under WHO targets would require tripling global periodontal expenditure-a level unlikely to be feasible-highlighting the need to rethink current models of periodontal care delivery.
Europe's "oncology industrial complex" (OIC) is the interconnected system linking cancer research, regulation, economic evaluation, and service delivery within largely publicly funded health systems. In 2020, an estimated 2.7 million people in the 27 member states of the European Union were diagnosed with cancer and 1.3 million died. The financial footprint is large, total cancer costs across Europe were estimated at €199 billion in 2018 and oncology medicine spending at list prices increased from €24.9 billion (2014) to €64.3 billion (2023). Yet spending growth does not automatically translate into patient benefit when real-world capacity (e.g., timely biomarker testing, workforce, radiotherapy infrastructure) constrains implementation. We argue that stewardship should align expenditure with deliverable care pathways by tying reimbursement to funded diagnostic and service capacity, institutionalising post-marketing outcome evaluation using interoperable data, publishing transparent capacity dashboards, and actively withdrawing low-value practices so that public investment yields measurable outcomes that matter to patients, including survival and quality of life.
Air pollution is a risk factor for dementia, but its role in early cognitive dysfunction is not clear. We aimed to investigate the association of air pollution with cognitive function, and the role of cardiovascular risk factors and greenspace in this association. The CAHHM (Canadian Alliance for Healthy Hearts and Minds Cohort Study) is a cohort of Canadian adults recruited between 2014 and 2018, for whom averages of exposures to NO2 and fine particulate matter were estimated for 5 years before recruitment. Outcomes included the Montréal Cognitive Assessment and Digit Symbol Substitution Test for cognitive function, and magnetic resonance imaging-measured covert vascular brain injury. Generalized linear mixed models assessed pollutant associations with outcomes in this cross-sectional analysis. A total of 6878 adults participated in the study, with a mean age of 57.6 years (SD=8.8), and 55.6% were women. Mean (SD; range) 5-year pollutant concentrations preceding enrollment for fine particulate matter were 6.9 μg/m3 (2.0 [1.8-11.2]), and for NO2 were 12.9 parts per billion (5.9 [0.9-33.9]). In adjusted models, a 5 μg/m3 higher fine particulate matter concentration was associated with 0.44 points lower Montréal Cognitive Assessment (95% CI, -0.62 to -0.25) and 1.31 points lower Digit Symbol Substitution Test (95% CI, -2.41 to -0.22) scores. A 5 parts per billion higher NO2 concentration was associated with 0.12 points lower Montréal Cognitive Assessment (95% CI, -0.17 to -0.07) and 0.38 points lower Digit Symbol Substitution Test (95% CI, -0.70 to -0.05) scores. A 5 parts per billion higher NO2 concentration was associated with higher odds of covert vascular brain injury (adjusted odds ratio, 1.08 [95% CI, 1.00-1.17]). Cardiovascular risk factors and greenspace did not change these associations. Fine particulate matter and NO2 were associated with lower cognitive function scores in middle-aged adults living in Canada, independent of cardiovascular risk factors. Our results warrant longitudinal follow-up to study the impact of air pollution on cognitive decline.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition associated with functional impairment and a relevant socioeconomic burden. While direct healthcare costs have been partially described in Spain, indirect costs related to loss of work productivity remain insufficiently characterized. This study aimed to estimate the indirect costs associated with CRSwNP in Spain from a societal perspective, focusing on productivity losses due to absenteeism and presenteeism. A cost-of-illness analysis with a one-year time horizon and a societal perspective was conducted in working-age adults (18-64 years) with CRSwNP in Spain. Disease prevalence (0.8%) was derived from national epidemiological studies. Productivity loss was estimated using published data on absenteeism and presenteeism, assuming a mean of 49.8 equivalent lost productivity days per patient per year. Economic valuation followed the human capital approach, applying average total labor costs and adjusting for labor market participation. Deterministic sensitivity analyses explored parameter uncertainty. An estimated 242,582 working-age adults were affected by CRSwNP, of whom 169,808 were effectively employed. The mean annual indirect cost per employed patient was €8,178.65, with presenteeism accounting for 60% and absenteeism for 40%. Extrapolation to the national level resulted in an estimated annual productivity loss of €1.39 billion, ranging from approximately €0.9 billion to nearly €2.0 billion in sensitivity analyses. CRSwNP is associated with substantial productivity losses in Spain, leading to a considerable indirect economic burden predominantly driven by presenteeism. These findings support the inclusion of indirect costs in assessments of disease burden and healthcare decision-making.
Academic medicine faces a workforce challenge. Experienced women physicians leave or disengage at disproportionate rates during their most productive years. We propose that the menopause transition, typically occurring between ages 40 and 55, converges with established sex inequities to create a predictable yet largely ignored driver of academic medicine attrition. Based on available data from meta-analyses, randomized trials, and longitudinal studies, we argue that menopause functions not merely as a symptom cluster to endure but as a catalyst for chronic disease that compounds workplace demands. Menopausal symptoms cost an estimated $1.8 billion annually in lost work time in the United States alone, with additional billions in medical expenses. Organizational interventions outperform individual-focused approaches in reducing burnout, with effect sizes nearly three times larger. Workplace-based cognitive behavioral therapy and coaching programs for women faculty have shown substantial benefits in randomized trials and cohort studies. We recommend universal design policies, coaching programs, structured mentorship, and systematic outcome tracking. With physician shortages projected to exceed 50,000 by 2033, supporting midcareer women through these natural biological transitions is both an ethical imperative and an institutional necessity.
To determine national health care expenditures associated with sleep disorders among children and adolescents in the United States. We conducted secondary analyses of the 2017-2022 Medical Expenditure Panel Survey (MEPS), including children 0-18 years of age (n = 41,384). Children with sleep disorders were identified by International Classification of Diseases, 10th Revision code G47.x. Multivariate two-part models, adjusting for covariates, were used to estimate associations between sleep disorders and health care expenditures. Among MEPS participants, on average 1.1% (95% CI: 0.9-1.3%) were diagnosed with a sleep disorder, representing 855,000 children diagnosed nationwide each year. Children with sleep disorders were more likely to be White, non-Hispanic (66.2%), categorized as having poor/near poor income (31.8%), on public insurance only (60.2%), and have significantly higher values on pediatric comorbidity index scores (2.7 vs. 0.3). The presence of a sleep disorder was associated with $3240 (95% CI: $2060-$4421, p < 0.0001) in incremental health care expenditures as compared to not having a sleep disorder ($5897 versus $2656), after controlling for predisposing, enabling, and need factors. National expenditures associated with childhood sleep disorders were estimated at $2.88 billion annually. Childhood sleep disorders exert a significant economic burden on society. Our analyses likely underestimate the total economic costs associated with childhood sleep disorders. Although the varied health outcomes of childhood sleep disorders are well understood, the national economic impacts of these disorders are poorly described. This information is important, as the estimated prevalence of these disorders in the pediatric population is high, and understanding the cost of these disorders could provide support for efforts promoting their early diagnosis and treatment. We found that the incremental health care costs associated with childhood sleep disorders were significant, amounting to $2.88 billion in annual expenditures. This high cost highlights the need for more effective strategies to prevent and manage pediatric sleep disorders.
Micronutrient deficiencies during pregnancy have serious consequences for both mother and child; thus the longstanding standard of care in low- and low-middle income countries (LMICs) has been daily prenatal iron-folic acid (IFA) supplementation. While prenatal multiple micronutrient supplements (MMSs) provide additional significant benefits in comparison to IFA supplements, the view that MMS is too expensive has hindered national MMS adoption. However, increased competition, volume procurement and the use of advanced purchase commitments have significantly reduced the cost of MMS. Using new cost data, we estimate the benefits of replacing IFA with MMS in both health (averted low birth weights (LBWs), stillbirths and female neonatal mortality) and monetary (costs of averted LBW and death; total economic value; benefit-cost ratios) terms in 25 LMICs with the greatest burden of LBW. A number of scenarios describing different coverage and procurement cost scenarios are explored. Replacing preventive antenatal IFA with MMS would avert 3 514 594 LBW births, 186 369 stillbirths and 218 914 female neonatal deaths over 5 years in these countries. Providing MMS to all pregnant women receiving at least one antenatal care visit averts 7 272 320 LBW, 473 471 stillbirths and 541 591 female neonatal deaths. The total cost of replacing IFA with MMS ranges from US$201.8 million to US$1.326 billion, equivalent to between 0.5% and 3.0% of current spending on efforts to reduce undernutrition. Using the most conservative estimate, this would generate US$7.19 billion in economic returns and a benefit-cost ratio greater than 10. The cost of averting a stillbirth or neonatal death ranges from US$497 to US$1306. Replacing prenatal IFA with MMS cost-effectively generates large health benefits.
Ambient fine particulate matter (PM2.5) was responsible for approximately 4.9 million deaths globally in 2023; however, empirical evidence on PM2.5-attributable health impacts remains sparse in Vietnam's Mekong Delta. This study quantified PM2.5 concentrations and estimated attributable mortality and economic burden in Can Tho City, Vietnam, for 2023. The study utilized satellite-derived PM2.5 estimates at 1 × 1 km resolution combined with local mortality data. Attributable deaths were calculated using the Global Exposure Mortality Model across six health endpoints, including ischemic heart disease (IHD), stroke, chronic obstructive pulmonary disease (COPD), lung cancer, lower respiratory infections (LRI), and non-communicable diseases plus lower respiratory infections (NCD + LRI). Economic losses were monetized using a Vietnam-specific Value of Statistical Life (VSL) derived through benefit transfer from the U.S. Environmental Protection Agency and the Organization for Economic Co-operation and Development, yielding VSL estimates of 10.4 and 6.8 billion VND, respectively. The annual mean PM2.5 concentration was 27.7 μg/m3, 5.5-fold higher than the World Health Organization guideline (5 μg/m3) and exceeding the Vietnamese national standard (25 μg/m3). Among 3417 NCD + LRI deaths in adults aged 25+ in 2023, 705 (95% CI: 546-828) were attributable to PM2.5, representing more than one in five deaths (20.6%) in this category (88 deaths per 100,000 population). Economic losses ranged from 3713 to 8611 billion VND, accounting for 3-7% of Can Tho City's gross regional domestic product. These findings demonstrate that PM2.5 pollution imposes a substantial health and economic burden on Can Tho City and provide robust quantitative evidence to support air quality management strategies in the Mekong Delta region.
Biological systems execute discrete, often irreversible actions - from DNA replication and cell-state transitions to Venus flytrap closure, vertebrate sex change, and human symbolic behavior - not as graded responses to single variables but as threshold-governed events emerging from the convergence of multiple necessary conditions. Here we formalize this convergence logic as the ARCH × Φ framework: a multiplicative threshold function in which Archetype (A, the conserved structural substrate), Drive (D, the energetic or hormonal activation), Context (C, the releasing stimulus or social cue), and Gating Field (Φ, a sterol-modulated permissiveness variable) must jointly exceed a system-specific commitment threshold θ. The multiplicative structure enforces a zero-term veto: suppression of any single component collapses execution regardless of the state of the other three. We trace the physical origin of Φ to the incorporation of sterols into eukaryotic membranes approximately 2.4 billion years ago, at the Great Oxidation Event, when oxygen-dependent sterol biosynthesis first separated stored electrochemical drive from discharge permissiveness - two quantities physically coupled in all pre-sterol membrane systems and independently tunable only with the arrival of the cholesterol ring structure. We propose that Φ is instantiated across three cholesterol-derived tiers: rapid modulation through accessible cholesterol pools and their oxysterol derivatives, intermediate modulation through neurosteroids synthesized via mitochondrial pathways, and lifetime-scale modulation through structural cholesterol deployment in myelin and perineuronal nets - all expressions of a single biophysical mechanism. We extend this account to two additional isoprenoid-based Φ systems: non-photochemical quenching (NPQ) in plant chloroplasts, where zeaxanthin and the PsbS protein constitute a zero-term veto gate for light-energy dissipation that is characterized to picosecond resolution, and insect holometabolous metamorphosis, where juvenile hormone functions as a Φ-suppressor and the dietary sterol auxotrophy of insects produces an environmentally gated Φ architecture distinct from the endogenous sterol synthesis of vertebrates. Monogenic Φ-lock disorders - exemplified by Niemann-Pick type C disease, in which disrupted intracellular cholesterol trafficking abolishes KCNQ2/3-dependent inhibitory gating - provide pathological proof-of-concept for the Φ-lock failure mode at the molecular level. The framework is formally equivalent to the h inactivation variable derived independently by Hodgkin and Huxley from squid axon voltage-clamp data in 1952, implying that Φ is not solely a theoretical construct but a measurable property of excitable membranes with a 2.4-billion-year evolutionary history. Explicit, falsifiable predictions are derived regarding perturbation-matrix experiments, CYP46A1 polymorphism effects on behavioral thresholds, the correlation of sterol enzyme diversity with behavioral plasticity rather than execution speed across taxa, dietary sterol auxotrophy and insect developmental plasticity, and τΦ acceleration as a route to increased biological output yield.
Domestic cats (Felis catus) are among the most popular pets in the world, with the global domestic cat population generally estimated to exceed 600 million and potentially approach 1 billion when feral populations are included. As hypercarnivores, cats exhibit unique metabolic deficiencies, particularly in phase II conjugation enzymes (e.g., glucuronidation, glycine conjugation), which impair elimination of phenolic xenobiotics including pharmaceuticals, feed additives, and contaminants. Consequently, the European Food Safety Authority (EFSA) Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) recommends an additional default uncertainty factor (UF) of 5 for such compounds. Physiologically based kinetic (PBK) modelling offers a mechanistic approach to refine these default factors using chemical-specific kinetic data and such models for the domestic cat are not currently available to the scientific and risk assessment community. Hence, this manuscript focuses on the development and validation of a generic PBK model for the species Felis catus according to the six-step process from the template of the Organisation for Economic Cooperation and Development (OECD) guidance document on characterisation, validation and reporting of PBK models for regulatory purposes. The model integrates meta-analysed physiological parameters from the peer-reviewed literature and 11 perfusion limited compartments. The model has been validated using chemical-specific inputs for 15 pharmaceuticals using in vitro and in vivo clearances to compare in vivo to in vivo and in vitro to in vivo predictions with the available experimental data for plasma maximum concentration (Cmax) and area-under-the-curve (AUC) values in blood after oral and intravenous exposure. Impact of bioavailability on model performance has also been assessed using conservative default values and reported or estimated values. In addition, global sensitivity analysis using the Sobol method identified the muscle:blood partition coefficient as the dominant parameter influencing model output variance. Overall, the generic PBK cat model performed well and most predictions accounting for bioavailability using in vitro derived clearance yielded 86% of Cmax predictions and 64% of AUC predictions were within 2 to 3-fold of the experimental data as recommended by the OECD. Future applications and refinements of the model with regard to NGRA of food and feed chemicals are highlighted.
Soil salinization impacts over one billion hectares, threatening global food security. Here, a salt-tolerant bacterial strain, Pseudomonas fluorescens G3, was isolated from the rhizosphere of maize (Jinongyu-719) growing in saline-alkali soils in Gansu Province, China. This strain demonstrated the ability to secrete indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, and extracellular polysaccharides. It also exhibited notable phosphate-solubilizing activity and robust siderophore production capabilities. Under salt stress conditions (200 mM NaCl), the P. fluorescens G3 strain significantly improved maize's growth parameters, namely its plant height, root length, and dry weight. Further, it enhanced antioxidant enzyme activity while reducing the accumulation of malondialdehyde (MDA), mitigating stress-induced oxidative damage. In P. fluorescens G3-inoculated plants, leaf and root Na+ contents decreased by 34.90% and 33.91%, while their K+ contents increased by 40.20% and 33.47%, respectively. Inoculation with P. fluorescens G3 enhanced taxonomic richness (ACE, Chao1) and evenness (Shannon, Simpson) in the rhizosphere bacterial community, leading to a significantly greater relative abundance of several bacterial genera: Pseudomonas, Methylophaga, Enhygromyxa, Desulfuromonas, and Devosia. These shifts in the microbial community composition suggest a potential restructuring of functional profiles, possibly enhancing processes beneficial to plant salt tolerance, such as ion homeostasis and stress mitigation: the biosynthesis of cofactors and secondary metabolites; bacterial secretion and two-component systems; porphyrin metabolism; flagellar assembly; biofilm formation; and bacterial chemotaxis. Redundancy analysis revealed positive correlations between microbial composition at both the phylum and genus levels and the activity of stress resistance enzymes after treatment with Pseudomonas fluorescens. This study provides important theoretical foundations and microbial resources for utilizing microbial community regulation in saline-alkali soil bioremediation.
Mental health care is increasingly delivered in primary care settings in the United States, yet referral patterns from non-psychiatric physicians to other providers remain incompletely described. The objective of this study is to examine demographic and clinical factors associated with referral to another physician during adult ambulatory visits to non-psychiatric physicians. A cross-sectional secondary analysis was conducted using the National Ambulatory Medical Care Survey from 2010 through 2015. The study included visits by adults aged 18 years and older to non-psychiatric physicians. Depression was identified using the survey indicator for current depression. The primary outcome was referral to another physician during the visit. Survey weighted logistic regression accounting for survey settings was utilized.  The final sample included 150,287 visits, representing 3.86 billion weighted visits nationally. In unadjusted analysis, depression was associated with higher odds of referral (OR = 1.31; 95% CI: 1.17-1.47; p < 0.001). In adjusted analysis, this association was reduced and remained non-significant (aOR = 1.13; 95% CI: 1.00-1.27; p = 0.051). Greater chronic disease burden and racial and ethnic minority status were independently associated with referral.  Referral during adult ambulatory visits reflects patient complexity and demographic factors, while depression alone was not independently associated with referral after adjustment.
All over the world, individuals are worried about the availability of safe drinking water and sanitation. According to the United Nations, there are billions of people who do not have access to clean drinking water. If not adequately treated, wastewater from industrial, domestic, and agricultural operations can harm water quality, human health, and aquatic ecosystems. Electrochemical wastewater treatment technologies are effective, selective, and disinfect in-situ because of their electrochemical nature. This study aimed to assess the usability and effectiveness of indirect-electrochemical oxidation (IEO) methods for distillery industrial wastewater (DIW) by measuring treatment efficiency and consumption of electrical energy (CEE). The impact of operational parameters, such as current (0.07-3.4 Amp), pH (3-11), chemical oxygen demand (COD) (500-2500 mg L-1), supporting electrolyte concentration (SEC) (2-10 g L-1), types of electrolyte (NaCl, KCl, Na2SO4, and Na2CO3), and electrode gap (2-4 cm), on the removal of % COD and CEE were investigated. The most effective electrolyte was found to be NaCl. The experiments with COD = 1000 mg L-1, SEC = 6 g L-1, stirring speed (SS) = 300 rpm, electrode gap (EG) = 2 cm, current = 0.27 Amp, and pH = 6 were established as the optimum level. For these conditions, it was observed that the COD removal was 85% and CEE was 19.38 kWhr kg COD-1, respectively. After a period of 6 h of operation, it has been observed that the IEO process offers a significant removal efficiency with respect to the parameters of operation for wastewater. The UV/Vis-spectrophotometer was employed to evaluate the color removal and oxidation of organic compounds. As a result of the experimental results, the IEO process appears to be a better technology for eliminating contaminants from wastewater while using required electrical energy.
Household air pollution (HAP) is a major environmental risk factor affecting nearly 3 billion people worldwide, and is strongly associated with cataract formation. However, the temporal dynamic and future trends of the global cataract burden attributable specific to HAP remain insufficiently understood. Unlike previous studies focusing on the overall cataract burden, this study quantifies the independent contribution of HAP as an intervenable environmental risk factor. Using data from the Global Burden of Disease database, we assessed global, regional, and national cataract burden attributable to HAP from 1990 to 2021. Joinpoint regression evaluated temporal trends, Age-Period-Cohort modeling elucidated drivers of burden changes, and health inequality was examined. Future burden was projected using ARIMA and ARIMA-LSTM hybrid models. In 2021, global HAP-attributable cataract burden reached 1956.32 thousand years lived with disability (YLDs), with age-standardized YLDs rate (ASYR) of 22.84 per 100,000. From 1990 to 2021, global YLDs increased steadily, with females consistently exhibiting higher burden than males, while ASYR declined. South Asia and East Asia bore the highest burden, with low socio-demographic index (SDI) regions most affected. Forecasts indicate global YLDs will rise to 1987.94 thousand by 2035, although ASYR will continue declining. HAP is strongly associated with cataracts globally. Females and people living in low-SDI regions are disproportionately affected. There is an urgent need to strengthen clean energy promotion, public health education, and targeted prevention programs in high-burden settings to reduce the cataract burden attributed to HAP.
Neglected tropical diseases (NTDs) are a group of 21 conditions affecting an estimated 1 billion people worldwide, causing significant mortality and morbidity. WHO has targeted their control, elimination or eradication by 2030, while highlighting that conflict and humanitarian emergencies are risks to achieving this. A systematic review of peer-reviewed literature was undertaken, using terms related to conflict-related humanitarian emergencies (CRHE), based on the Armed Conflict Location & Event Data Project codebook terms for defining emergencies and terms including all WHO-defined NTDs. After a two-stage screening process, 26 papers were included. Common challenges for NTD programmes in CRHE were healthcare access, infrastructure, population movement and data quality. Multisectoral collaboration between actors in conflict-settings was offered as a learning for NTD programmes, along with community participation and decentralisation. Evidence gaps were identified in the knowledge base for certain NTDs and in high-quality evidence for interventions in CRHE. Collaboration is a key area for focused improvement for NTD programmes in CRHE. This should be across sectors and extend to research and analysis approaches, to ensure the most effective interventions are identified and implemented and that NTD road map targets can be achieved.
Multiple long-term conditions (MLTCs), or multimorbidity-the co-occurrence of multiple chronic conditions-present a growing challenge for primary care. Existing predictive models typically focus on single outcomes and often fail to capture the temporal and competing-risk structure inherent in longitudinal electronic health records (EHRs). Here, we present SurvivEHR, a generative transformer-based foundation model trained on over 7.6 billion coded events from 23 million patients in UK primary care. SurvivEHR is pre-trained using a competing-risk, time-to-next-event objective, enabling calibrated risk stratification across a broad range of diagnoses, investigations, medications, and mortality events. We show that this pre-training objective yields strong next-event discrimination and learns clinically meaningful patient trajectories. When adapted through fine-tuning, SurvivEHR achieves improved performance on downstream prognostic tasks, including longer-horizon risk prediction, with particular benefits in low-resource settings. By learning longitudinal patient representations directly from routine primary care records, SurvivEHR provides a scalable foundation for developing generalisable clinical risk models that reflect the complexity of MLTCs in primary care.
The first protein kinases and their role in cell regulation were identified in the mid-1950s, but it was not until the 1980s that the first inhibitors of these enzymes were developed. More specific inhibitors that suppressed kinase activity at low nanomolar concentrations were described in the mid-1990s and their potential to treat cancers caused by kinase mutation became clear during the late 1990s. Over 100 protein and lipid kinase inhibitors have now been approved for clinical use during the 21st century with combined annual sales of over US$ 65 billion in 2024. They have not only transformed the clinical care of multiple malignancies but have also been exploited widely to identify physiological substrates and cellular functions of these enzymes. Here, I present some personal reflections on the early days of kinases and their inhibitors, give a few examples of how they were first exploited to dissect signal transduction pathways and explain how the first panels of protein kinases came to be established to facilitate the development of more specific kinase inhibitors.
How do thousands of cell-surface proteins specify billions of neuronal connections in developing brains? We previously found that inverse expression of a ligand-receptor pair, teneurin-3 (Ten3) and latrophilin-2 (Lphn2), in CA1 and subiculum, instructs CA1→subiculum target selection through Ten3-Ten3 homophilic attraction and Ten3-Lphn2 heterophilic reciprocal repulsions. Here, we leveraged conditional knockouts to demonstrate that these mechanisms generalize to several nodes of the extended hippocampal networks, including entorhinal cortex and hypothalamus. Cooperation between attraction and repulsion may differ depending on the order in which developing axons encounter the attractant and repellent subfields. Ten3 and Lphn2 can serve as both ligands for incoming axons and as receptors for their own target selection within the same neuron; Ten3 can be repulsive or attractive as a ligand or receptor. Thus, multifunctionality and repeated use, together with recurrent circuit motifs prevalent in the brain, enable one ligand-receptor pair to instruct target selection of many neurons.