Sudden cardiac death (SCD) causes 4 to 5 million deaths each year globally. Electrical vortices (tornadoes or rotors) are the origin of ventricular fibrillation (VF), which often causes SCD. Cardiac electrical vortices have complex dynamics and have been shown in many mammalian species. During VF, the heart fails to contract suitably and is unable to pump blood. Once VF is initiated, drug treatments are ineffective and even make things worse. The only effective treatment is electrical shock to the ventricles. Our current understanding of VF mechanisms is fragmentary, hindering the development of personalized therapies. Yet recent insights into the roles of the most critical sarcolemmal ion channels in VF in controlling the excitation-recovery process provide hope. Substantial evidence indicates that the molecular interplay between the main cardiac sodium channel (NaV1.5) and the strong inward-rectifier potassium current (Kir2.1) controls cardiac excitability, wave propagation velocity, and rotor formation, as well as rotor stability and frequency during VF. Studies at the cellular, molecular, and ion channel levels are helping us understand how rotors generate the turbulence that characterizes VF, providing insights into how to prevent their initiation and identifying new therapeutic targets to avert premature death.
Increasing evidence links exposure to extreme weather events in utero with adverse health outcomes at birth, including lower birth weight. This research, however, often faces data limitations because natural disasters may be localized, often affecting some neighborhoods but not others, whereas outcome data are often available only at higher geographic levels, such as counties. In this article, we introduce a novel strategy for estimating the effects of geographically bounded disasters when localized outcome data are unavailable. We employ this strategy to estimate the effect of exposure to severe tornadoes on infant birth weight in the United States from 1991 to 2017. We merge county-month data on singleton births with block-group-level monthly data on the paths of severe tornadoes and block-group data on the distribution of the population at risk of a birth. We then estimate difference-in-differences models in which the treatment variable is equal to the percentage of the population at risk of a birth affected by the tornado. This strategy results in an estimand that is both more interpretable and more policy-relevant than estimands from traditional models. Our findings demonstrate that exposure to a tornado during pregnancy reduced birth weight for Black mothers.
Pediatric data on health care utilization following disasters are limited, with most studies focused on adults. This study evaluated changes in pediatric emergency department (ED) volumes, hospital admissions, and diagnoses following Major Disaster Declarations by the Federal Emergency Management Agency. This was a retrospective observational analysis of patients aged ≤18 years presenting to a Pediatric Health Information System-participating ED between 2010 and 2023. We paired each Pediatric Health Information System ED with any major disaster that occurred within 50 miles of the ED. For each ED-disaster pair, we analyzed changes in weekly ED visits, admissions, and diagnoses for weeks 1 to 4 after the disaster. We report mean counts (SD) and percent changes (95% confidence interval), stratified by the 5 disaster types (severe storm/flood, snow/ice storm, fire, tornado, and earthquake). Across 288 Major Disaster Declarations over 14 years, there were 409 ED-disaster pairs. For all disaster types, ED visits and admissions showed modest week 1 declines followed by a return to baseline levels. Tornadoes were associated with consistent decreases in ED visits over all 4 weeks, whereas snow/ice storms, severe storms/floods, and earthquakes demonstrated early decreases followed by recovery. Fires were associated with sustained increases, particularly for respiratory diagnoses. Admissions declined after tornadoes, with smaller decreases after snow/ice storms and earthquakes, whereas remaining stable after severe storms/floods and fires. Pediatric ED utilization generally declined modestly after most disasters but increased following fires, driven by respiratory presentations. Declines likely reflect disruptions in access and care seeking, whereas fire-related surges highlight distinct respiratory effects. Preparedness efforts should incorporate event and diagnosis-specific trends to support continuity of operations and capacity for brief surges when they occur.
In recent decades, escalating extreme climate events (ECEs) have raised significant concerns regarding their effects on public health in South Africa, particularly respiratory illness. This study examined the relationship between ECEs and respiratory health outcomes over a 12-year period (2008-2019). A total of 48 ECEs were analyzed, of which 28 occurred in regions reporting more than 100 medical insurance claims for respiratory diseases. These events included storms, heatwaves, cold waves, floods, and tornadoes. Using a two-week lag period, we assessed their short-term association with respiratory claims. The findings revealed both increases and decreases in claims following ECEs, yet seasonal epidemiological trends exerted a more consistent and pronounced influence on respiratory health than individual extreme events. Percentage variations for statistically significant events ranged from approximately + 16% to + 121%, while decreases ranged from - 5% to - 178%. Although certain events displayed notable impacts, no distinct clustering was observed across seasons or years. These results underscore the importance of strengthening seasonal preparedness measures alongside climate-sensitive surveillance systems. Integrated approaches that address both seasonal and extreme climate risks are vital to safeguard vulnerable populations amid increasing climate variability in South Africa.
The growing threats of natural disasters influence human migration at various spatio-temporal scales. This study examines how the four major disaster types (i.e., floods, hurricanes, wildfires, and tornadoes) relate to human migration in the contiguous United States (CONUS) from 2000 to 2020. Utilizing statistical and machine learning methods, we quantify spatial and temporal variations in migration patterns in relation to disaster impacts while controlling for socio-economic and environmental variables. Results indicate that counties experiencing higher disaster impacts consistently show lower average net migration rates (NMR), with increased disaster frequency or damage often correlating with reduced migration rates. Using an automated machine learning (AutoML) framework, we developed predictive models that can explain 59% to 72% of the variance in county-level NMR, significantly outperforming benchmark linear regression models. SHapley Additive exPlanations (SHAP) values were used to assess the contribution of disaster and socio-economic variables to model predictions. Although socio-economic factors remain the dominant predictors, hurricanes, floods, and wildfires showed substantial associations with migration patterns over the two decades. Overall, this study demonstrates the value of explainable AI in capturing the complex dynamics between natural disasters and human migration, offering insights into how disasters and socio-economic factors are jointly associated with population movement.
The spontaneous emergence of macroscopic dissipative structures in systems driven by generalized chemical potentials is well established in non-equilibrium thermodynamics. Examples include atmospheric/oceanic currents, hurricanes and tornadoes, Rayleigh-Bénard convection cells and reaction-diffusion patterns. Less well recognized, however, are microscopic dissipative structures that form when the driving potential excites internal molecular degrees of freedom (electronic states and nuclear coordinates), typically via high-energy photons or coupling with ATP. Examples include dynamic nanoscale lipid rafts, kinesin or dynein motors along microtubules, and spatiotemporal Ca2+ signaling waves propagating through the cytoplasm. The thermodynamic dissipation theory of the origin of life asserts that the core biomolecules of all three domains of life originated as self-organized molecular dissipative structures-chromophores or pigments-that proliferated on the Archean ocean surface to absorb and dissipate the intense "soft" UV-C (205-280 nm) and UV-B (280-315 nm) solar flux into heat. Thermodynamic coupling to ancillary antenna and surface-anchoring molecules subsequently increased photon dissipation and enabled more complex dissipative processes, including photosynthesis, to dissipate lower-energy but higher-intensity UV-A and visible light. Further thermodynamic coupling to abiotic geophysical cycles (e.g., the water cycle, winds, and ocean currents) ultimately led to today's biosphere, efficiently dissipating the incident solar spectrum well into the infrared. This paper reviews historical considerations of UV light in life's origin and our proposal of UV-C molecular dissipative structuring of three classes of fundamental biomolecules: nucleobases, fatty acids, and pigments. Increases in structural complexity and assembly into larger complexes are shown to be driven by the thermodynamic imperative of enhancing solar photon dissipation. We conclude that thermodynamic selection of dissipative structures, rather than Darwinian natural selection, is the fundamental creative force in biology at all levels of hierarchy.
High-dose methotrexate (HDMTX) is a key treatment for lymphoma with central nervous system involvement. Whether incorporating cystatin C into glomerular filtration rate estimation improves methotrexate (MTX) clearance prediction remains unclear. We aimed to evaluate whether cystatin C-inclusive glomerular filtration rate equations improve MTX clearance prediction and to explore the relationship between MTX exposure and acute kidney injury (AKI) in adult patients with lymphoma receiving HDMTX. This was a prospective single-center study performed on 80 adult patients with lymphoma receiving HDMTX (1.5-8 g/m2) over a 4-h infusion. A population pharmacokinetic model was constructed using data from 80 administrations of HDMTX and 427 serum MTX concentrations. The population pharmacokinetic model estimated MTX concentrations were included in a logistic regression to assess the relationship between MTX exposure and AKI. A two-compartment model best described the pharmacokinetic data, with baseline albumin and CKD-EPI creatinine-cystatin C (eGFRCr-CysC) as significant covariates on clearance. Seventeen patients (21%) developed any-stage AKI. Among those receiving ≤ 3.5 g/m2, model-estimated 4-h MTX concentrations were associated with AKI (odds ratio: 1.02 per µmol/L; p = 0.0038), with an optimal threshold of 160 µmol/L (area under the concentration-time curve: 0.818). Patients above this threshold were 22 times more likely to experience AKI (p = 0.0005). This association was not observed in patients treated with 8 g/m2. Despite a lower dose and exposure, patients receiving ≤ 3.5 g/m2 demonstrated a stronger concentration-toxicity relationship. Our results support the use of cystatin C-inclusive glomerular filtration rate estimates in MTX pharmacokinetic modeling and suggest early MTX concentration sampling may identify AKI risk, enabling proactive, AKI-mitigating clinical interventions during HDMTX therapy.
Natural disasters and emergency situations, such as a massive cyberattacks can occur without warning and can impact academic operations, including experiential education. Weather-related catastrophes like hurricanes, tornados, flooding, and forest fires, require action to support students, preceptors, and communities, while cyberattacks and other challenges to technological infrastructure require similarly coordinated responses. Often, a "perfect storm" of circumstances leads to compounding issues and associated challenges for experiential educational operations, while also impacting local populations and the health systems that are providing critical healthcare for impacted communities. The time-sensitive nature of responding to disasters can often rush pharmacy faculty and administrators into urgent hasty decision making, when disaster response needs planning to ensure that all parties come out ahead in the long-term. Decisions and efforts can be informed by previous emergent situations and the wisdom gained from others across the Academy. Herein we provide reflections from multiple PharmD educational programs experiencing recent, large-scale disasters and provide approaches for aiding experiential education teams in responding to disasters safely, efficiently, and effectively.
Extended reality (XR), a stereoscopic three-dimensional visualization technique (3DVT), enables 3D and four-dimensional (4D) cardiac visualization and can improve spatial understanding of anatomy and hemodynamics in congenital heart disease. Four-dimensional flow magnetic resonance imaging data from 2 Fontan patients was visualized using the HoloLens, an immersive and interactive 3DVT that allowed users to explore the 4D model and select various flow effects. Complex flow patterns-such as tornado-like coiling and helical flows-provided insights into abnormal hemodynamics. Monoscopic 3DVT may hinder accurate interpretation of 4D data, especially in users with lower visual-spatial abilities (VSA). XR supports these users by making 4D data more intuitive to interpret, enabling performance comparable to those with higher VSA and thereby enhancing clinical data interpretation and decision-making. With interactive 3D/4D models, XR can facilitate a more intuitive and accurate interpretation of clinical data, allowing users with lower VSA to achieve performance levels comparable to those with higher VSA.
People have been increasingly using social media to post messages during a natural disaster, and describe the locations of victims, damages, difficult situations, and relief resources. Many of these location descriptions are in the forms of detailed and multi-entity descriptions, such as door number addresses, road intersections, and highway exits. Currently, there is limited availability of datasets that contain these detailed location descriptions labeled in disaster-related messages. A lack of these datasets hinders the understanding of how people describe locations during disasters and the automatic extraction of these location descriptions. This paper fills this gap by providing a dataset that covers ten disasters in the United States and in five disaster types: hurricanes, floods, wildfires, tornados, and winter storms. The messages containing location descriptions are collected from the social media platform Twitter/X, and we describe the collection, labeling, and validation of this dataset. This dataset can be used for studying the ways people describe locations under disaster contexts and for training AI models to extract these important locations.
To assess the sustained, long-term efficacy of bimekizumab in improving patient symptoms and health-related quality of life (HRQoL) in axial spondyloarthritis (axSpA) to 3 years. Both BE MOBILE 1 (non-radiographic axSpA) and 2 (radiographic axSpA) comprised a 16-week double-blind, placebo-controlled treatment period and a 36-week maintenance period. From week 16, all patients received subcutaneous bimekizumab 160 mg every 4 weeks. At week 52, eligible patients could enter the open-label extension (OLE), BE MOVING and continue bimekizumab treatment. Here, we report pooled results for changes in spinal pain, morning stiffness (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Q5 and Q6), physical function (Bath Ankylosing Spondylitis Functional Index (BASFI)), fatigue (BASDAI Q1 and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue), sleep quality (Medical Outcomes Study Sleep (MOS-Sleep-R) Index II) and HRQoL (36-Item Short Form Questionnaire (SF-36) Physical Component Summary (PCS)/Mental Component Summary; Ankylosing Spondylitis Quality of Life (ASQoL)) to 3 years in the overall study population; for spinal pain and physical function, patient-level data are also reported. Of the 494/586 (84.3%) randomised patients who entered the OLE, 425/494 (86.0%) completed week 164. At week 164, patients reported mean improvements from baseline in total (-4.3) and nocturnal (-4.3) spinal pain, morning stiffness (-4.3), physical function (BASFI: -2.9), fatigue (BASDAI Q1: -3.5, FACIT-Fatigue: +9.7), sleep (MOS-Sleep-R Index II: +10.8) and HRQoL (SF-36 PCS: +12.3; ASQoL: -5.6). Rapid and sustained patient-level improvements to week 164 in spinal pain and physical function levels were observed. Bimekizumab treatment led to rapid and sustained improvements in key patient symptoms and HRQoL to 3 years, emphasising its long-term value in controlling symptoms which profoundly affect patients' experience and daily lives. BE MOBILE 1 (NCT03928704), BE MOBILE 2 (NCT03928743) and BE MOVING (NCT04436640).
Neonatal Respiratory Distress Syndrome (NRDS) is the most common cause of hospitalization and preterm birth and one of the leading causes of death in newborns. The main intervention is surfactant therapy. This study aimed to determine the cost-effectiveness of Calfactant compared to Beractant and Poractant alfa in treating preterm infants with RDS in Iran. A two-state decision tree model was developed based on RDS disease pathways, assuming that neonates had been admitted to the NICU using one of the aforementioned surfactants. Efficacy as life years gained (LYG) and transition probabilities between states were extracted from international RCTs. Costs are presented in US dollars, and the incremental cost-effectiveness ratio (ICER) is presented from the Iranian healthcare system perspective. To evaluate the model’s robustness against data uncertainties, the study conducted both deterministic (one-way and two-way) and probabilistic sensitivity analyses, including a Monte Carlo simulation, using varied input ranges and distributional modeling, with results visualized through tornado plots and scatter plots. From the Iranian healthcare system perspective, in RDS preterm neonates, Calfactant was cost-effective versus Beractant. However, it is not cost-effective compared to Poractant alfa.
In the UK, a parent dies every 22 minutes, significantly affecting children's mental health, education, and social well-being. Yet little is known about children's lived experiences of bereavement and support. Developed with public involvement, this qualitative study employed constructivist grounded theory. In-depth virtual interviews were conducted with eleven parentally bereaved children aged ten to eighteen. Iterative data analysis used the constant comparative method. Analysis constructed five themes: (1) What helps, (2) Talking on your terms, (3) A tornado of emotions, (4) Difficulties accessing support, and (5) Stepping up at home. Participants reported value when involved in family matters but often concealed emotions to protect others. Friendships were strained, and participants felt forgotten and pressured to "move on" over time. Some children struggle to discuss parental death for fear of burdening others. Greater societal awareness and sustained, sensitive support are vital to navigate life without a parent.
This study, based on Complex Adaptive Systems theory and the "4C" framework, explores the dynamics of information sharing and collaboration networks within China's emergency management system during disasters. It rigorously explores the nuances in the connections and differences between these networks. Employing Social Network Analysis (SNA) and Temporal Exponential Random Graph Models (TERGMs), the research scrutinizes the relationships of disaster information sharing and collaboration among local public departments in the aftermath of the 2016 Funing tornado in Jiangsu, China. This study is dedicated to understanding how these networks evolve within a hierarchical administrative framework. The findings underscore three pivotal trends in the evolution of information and collaboration networks: a reduction in network redundancy, localized strengthening in ties, and differential adaptations. These trends are instrumental in enhancing the broader understanding of emergency management. They spotlight the importance of efficient information dissemination and robust collaborative frameworks, particularly in the context of China's centralized and hierarchical emergency management structure.
Patients with extensive ischaemic change are often excluded from endovascular thrombectomy. We aimed to synthesise the evidence from recent trials in these patients by performing a systematic review and individual patient data meta-analysis to estimate treatment benefit, including within clinical and imaging subgroups. In this systematic review and meta-analysis, we searched PubMed and Embase for randomised trials published between March 1, 2018, and March 1, 2025, that evaluated efficacy and safety of endovascular thrombectomy compared with medical management in patients with large-core ischaemic stroke (based on an Alberta Stroke Program Early CT Score [ASPECTS] of ≤5 or estimated ischaemic core ≥50 mL) presenting within 24 h of onset. Individual patient-level data from all eligible trials were obtained. A central imaging core laboratory readjudicated ASPECTS and reanalysed ischaemic core volume. A two-stage meta-analysis with random-effects model was used to evaluate the distribution of 90-day modified Rankin Scale (mRS) scores (the primary outcome) using adjusted pooled generalised odds ratios (aGenORs). Missing data were handled by multiple imputation. Safety outcomes were all-cause mortality within 90-day follow-up and neurological worsening within 24-48 h of randomisation, reported as adjusted pooled relative risk (aRR); and symptomatic intracerebral haemorrhage within 36 h of randomisation (reported as risk difference). Subgroup analyses based on clinical and imaging characteristics were done, including subgroups defined by ischaemic core volume, ASPECTS, and time window from onset to randomisation. The meta-analysis was registered with PROSPERO (CRD420251058584). We included 1886 patients (944 assigned to endovascular thrombectomy and 942 assigned to medical management) from six trials. Baseline characteristics were similar between treatment groups. At day 90, the distribution of mRS scores was improved in patients in the endovascular thrombectomy group (median score 4 [IQR 3-6]; n=940) versus those in the medical management group (5 [4-6]; n=931; aGenOR 1·63 [95% CI 1·42-1·88], p<0·0001). The endovascular thrombectomy group also had reduced mortality (292 [31·1%]) compared with the medical management group (347 [37·3%]; aRR 0·82 [95% CI 0·70-0·97], p=0·022). No significant differences were observed in symptomatic intracranial haemorrhage (ten [1·1%] of 944 vs nine [1·0%] of 942 patients; pooled unadjusted risk difference -0·17 percentage points [95% CI -1·01 to 0·67], p=0·69) or neurological worsening (197 [22·0%] of 896 patients vs 161 [17·9%] of 899; aRR 1·19 [0·87-1·62], p=0·27). Improved functional outcomes with endovascular thrombectomy were consistent across clinical and imaging subgroups, except for those with an estimated ischaemic core volume of 150 mL or greater, in whom point estimates favoured endovascular thrombectomy, particularly in the early time window (0-6 h), but wide 95% CIs limited interpretation. Endovascular thrombectomy was associated with improved functional outcomes and reduced mortality versus medical management in patients with large-core ischaemic stroke presenting within 24 h of onset. With the exception of very extensive ischaemic changes (core volume ≥150 mL) presenting beyond 6 h, where evidence remains limited, benefit was sustained across ASPECTS and ischaemic core strata for patients presenting up to 24 h after onset. None.
The paper presents a comprehensive description of a new setup implemented and commissioned at the SEXTANTS beamline of Synchrotron SOLEIL for absorption and scattering experiments with X-ray beams carrying an orbital angular momentum, also known as twisted X-ray beams. Two alternative methods have been implemented, based on the use of either spiral zone plates or fork grating devices, and we show how they can be used for both defining and assessing the orbital angular momentum of an X-ray beam. We also demonstrate that cascading multiple devices enables integer operations on the orbital angular momentum of the resulting X-ray beam. Finally, we report the results of the first resonant scattering pilot experiments in transmission and reflection mode, intended to assess the feasibility of future users' measurements. The availability of twisted soft X-rays complements the range of experimental techniques in elastic, resonant and coherent scattering available at the SEXTANTS beamline.
Standard Community Assessment for Public Health Emergency Response (CASPER) methods, a type of rapid needs assessment (RNA) for collecting data on household needs and impacts following emergencies, are not always suitable for rural, destroyed, or severely damaged communities, or disasters affecting small geographical areas. The objectives of this modified RNA were to: (1) identify the strengths, limitations, and operational challenges for utilization of modified RNAs for post-disaster, quick response research; and (2) capture the acute mental and physical health impacts and lived experiences of communities affected by the 2024 Arbor Day tornado in Nebraska (USA). This field study tested modifications of the CASPER methodology in rural and inaccessible communities in Washington and Douglas County, Nebraska following the 2024 Arbor Day tornado. A 60-item survey was developed using validated questions, including on mental and physical health impacts. Survey completion rates for Washington and Douglas Counties were 57.3% and 89.3%, respectively. Exacerbation of existing conditions, worsening allergies, and stress were commonly reported following the tornado. Modified RNAs were useful and feasible approaches for capturing perishable data following the 2024 Arbor Day tornado outbreak. These findings can be used to inform not only public health response but also future planning and policy.
Implantable tibial nerve neuromodulation (ITNM) represents a minimally invasive intervention for urgency urinary incontinence (UUI). This study evaluated the 3-year cost-utility of ITNM with an external wearable battery (Revi System) versus conservative treatments (behavioral ± pharmacotherapy) from a US payer perspective. A cohort state-transition (Markov) model with annual cycles compared ITNM to conservative treatment modalities (behavioral ± pharmacotherapy). ITNM clinical parameters were derived from the OASIS pivotal trial (N = 150); parameter uncertainty was propagated via 20,000 Monte Carlo simulations. Health states captured responder and non-responder status with permitted transitions, rescue interventions (onabotulinumtoxinA, sacral neuromodulation, percutaneous tibial nerve stimulation), and downstream event modules (falls, urinary tract infection, incontinence-associated dermatitis, depression, cognitive decline/dementia, and nursing-home entry). Costs and quality-adjusted life-years (QALYs) were discounted at 3% annually and expressed in 2025 US dollars. Parameter uncertainty was assessed using probabilistic sensitivity analysis (PSA; 20,000 simulations) and tornado analysis. ITNM was both more effective and less costly than behavioral ± pharmacotherapy. Mean 3-year costs were $39,308 versus $43,737 (ΔCost = -$4,428), with mean QALYs of 2.188 and 1.940, respectively (ΔQALY = +0.249). The incremental cost-effectiveness ratio was -$17,818/QALY (dominant). Incremental net monetary benefit at $40,000/QALY was $14,369, with 100% probability of cost-effectiveness across thresholds from $20,000-$150,000/QALY. Key value drivers were responder utility and fall-related parameters. The analysis adopts a US payer perspective with direct medical costs only. Some event risks were applied from population-level sources and may not fully capture patient-level heterogeneity. The 3-year base-case horizon may miss longer-term durability effects, though extended-horizon scenarios support consistent findings. Over 3 years, ITNM with an external wearable battery improves quality-adjusted survival and lowers overall payer costs compared with conservative therapies for UUI, supporting its inclusion as a value-consistent minimally invasive therapy. Urgency urinary incontinence (UUI) is a condition in which people experience sudden, uncontrollable urges to urinate that result in leakage. It affects millions of adults and can lead to falls, skin problems, depression, and nursing home placement. Current treatments include bladder training, pelvic floor exercises, and medications, but most people stop their medications within the first year due to side-effects or limited improvement.Implantable tibial neuromodulation (ITNM) is a newer, minimally invasive option. A small device implanted near the ankle delivers gentle electrical signals, powered by an external wearable battery, to calm the nerves controlling bladder function. A large clinical trial found that about 78% of people treated with ITNM experienced meaningful symptom improvement.Researchers built a computer model to compare the costs and health outcomes of ITNM against conservative treatments over 3 years from the perspective of US health insurers. The model tracked direct treatment costs and costs of related health events such as falls, urinary tract infections, and long-term care.Results showed that ITNM both saved money and improved quality-of-life. Over 3 years, ITNM saved an average of $4,428 per person while providing roughly three additional months of quality-adjusted life. Although ITNM costs more in the first year due to the implant procedure, those costs are offset by fewer complications in the following years. These findings held across a wide range of assumptions, suggesting that ITNM offers good value for people with UUI who have not responded to standard treatments.
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