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Objectives: To summarize available data on unit costs for human immunodeficiency virus (HIV) testing, prevention, and care interventions in Latin America and the Caribbean. Methods: We conducted a systematic literature review of costing studies published between 2012 and 2024, and selected those reporting empirically measured costing data. The available data were categorized according to predefined intervention categories and compared by time and place. We also explored variations in unit costs by intervention type. Results: Of 1 746 studies identified, 22 met the inclusion criteria, which provided 103 unique unit cost estimates from nine countries. About 50% of the included studies were published between 2019 and 2021. Antiretroviral therapy services had the most cost data available (39% of unit costs), followed by inpatient care (27%) and HIV testing (24%). Considerable cost variations were observed both within and between interventions. Conclusions: Our analysis underscores the need for accurate and reliable cost data to support HIV budgeting and decision-making efforts. We identified several gaps in the availability of cost data and emphasize the importance of presenting results more effectively by incorporating key contextual variables. Given the challenges of shrinking budgets and sustainability risks, robust evidence is indispensable to inform priority setting and budget allocation for HIV services.

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Ballistic impacts on human thorax without penetration can produce severe injuries or even death of the carrier. Soft tissue finite element models must capture the non-linear elasticity and strain-rate dependence to accurately estimate the dynamic human mechanical response. The objective of this work is the calibration of a visco-hyperelastic model for soft tissue simulants. Material model parameters have been calculated by fitting experimental stress-strain relations obtained from the literature using genetic algorithms. Several parametric analyses have been carried out during the definition of the optimization algorithm. In this way, we were able to study different optimization strategies to improve the convergence and accuracy of the final result. Finally, the genetic algorithm has been applied to calibrate two different soft tissue simulants: ballistic gelatin and styrene-ethylene-butylene-styrene. The algorithm is able to calculate the constants for visco-hyperelastic constitutive equations with high accuracy. Regarding synthetic stress-strain curves, a short computational time has been shown when using the semi-free strategy, leading to high precision results in stress-strain curves. The algorithm developed in this work, whose code is included as supplementary material for the reader use, can be applied to calibrate visco-hyperelastic parameters from stress-strain relations under different strain rates. The semi-free relaxation time strategy has shown to obtain more accurate results and shorter convergence times than the other strategies studied. It has been also shown that the understanding of the constitutive models and the complexity of the stress-strain objective curves is crucial for the accuracy of the method.

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Background: There is limited real-world data of lipid control and healthcare costs among patients with and without Atherosclerotic Cardiovascular Disease (ASCVD) in Latin America. Methods: A retrospective cohort study including patients with LDL-cholesterol (LDL-C) assessment from 2015 to 2017 was performed in a health insurance database. Patient characteristics, comorbidities and laboratory data were collected, and International Classification of Diseases (ICD) codes were used to identify a subcohort of patients with ASCVD (secondary prevention) and assess the proportion of these patients with LDL-C controlled. Lipid control among patients without ASCVD (primary prevention) and healthcare costs in one year in the overall population were also assessed. Results: From the 17,434 patients selected, 5,208 (29.8%) had ASCVD. The mean age of these patients in secondary prevention was 68.9 (±12.3) years and 47.8% were male patients. LDL-C < 70 mg/dL was identified in 19.1% of the ASCVD population and only 4.1% had an LDL-C < 50 mg/dL. LDL control was worse in women compared to men (13.1% vs. 25.7%; P < 0.01). The average cost in one year was 3,591 American dollars (USD) per patient in primary prevention compared to 8,210 dollars per year for patients in secondary prevention (P < 0.01). While outpatient costs accounted for 59.8% of the total cost in the primary prevention group, the main cost of the secondary prevention population was related to hospital costs (54.1%). Conclusion: Despite the favorable evidence for intensive cholesterol reduction, the evaluation of large real-world database with more than 17,000 individuals showed that the targets of guideline recommendations have not yet been adequately incorporated into clinical practice. Average annual cost per patient in secondary prevention is more than twice compared to primary prevention. Hospital expenses account for most of the cost in the secondary prevention group, while outpatient costs predominate in primary prevention.

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We conducted a cluster-randomized hybrid effectiveness-implementation study of CyberRwanda, a digital family planning and reproductive health intervention for Rwandan adolescents. Sixty schools were randomized 1:1:1 to control or to one of two implementation models-self-service (self-guided access on tablets) or facilitated (peer-led clubs plus tablet access) with no masking. Eligible participants were aged 12-19 years, in secondary school levels 1 or 2, and willing to provide consent or assent/parental consent and contact information for follow-up. In 2021, 6,078 randomly selected adolescents were enrolled. At 24 months, 91.3% of participants were retained and included in the primary intention-to-treat analyses (control, n = 1,845; self-service, n = 1,849 and facilitated, n = 1,858). There were no adverse events related to the study. CyberRwanda did not affect the primary outcomes of modern contraceptive use (prevalence ratio (PR) = 1.04; 95% confidence interval (CI) = 0.76, 1.42), childbearing (PR = 1.33; 95% CI = 0.71, 2.50) and HIV testing (PR = 1.00; 95% CI = 0.91, 1.11) in the full sample. Significantly higher modern contraceptive use observed in the CyberRwanda facilitated arm in a prespecified analysis of sexually active participants suggests that longer-term evaluation is needed to examine effects as more of the study population becomes sexually active and has increased demand for contraception. ClinicalTrials.gov registration: NCT04198272 .

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INTRODUCTION: In patients with acute ischemic stroke (AIS) secondary to intracranial large vessel occlusion (LVO), optimal blood pressure (BP) management following endovascular treatment (EVT) has not yet been established. The randomized trial on Hemodynamic Optimization of cerebral Perfusion after successful Endovascular therapy in patients with acute ischemic stroke (HOPE) (clinicaltrials.gov id: NCT04892511), aims to demonstrate whether hemodynamic optimization using different systolic BP targets following EVT according to the degree of final recanalization, is more effective than currently recommended BP management in improving functional outcomes of patients with AIS. METHODS: HOPE is an investigator-initiated multicentre clinical trial with randomized allocation, open label treatment, and blinded endpoint evaluation (PROBE). Patients with an anterior circulation AIS within 24h of symptom onset, treated with EVT, and showing successful recanalization (mTICI ≥2b) at the end of the procedure, are equally allocated (1:1) to hemodynamic optimization according to the study protocol vs. BP management according to current guidelines (≤180/105mmHg). The protocol includes two different targets of systolic BP depending on the recanalization status (mTICI=2b: 140-160 mmHg; mTICI=2c/3: 100-140 mmHg). The protocol is applied within the first 72h and includes BP lowering as well as vasopressor therapies when needed. The primary outcome is the proportion of favorable outcome (modified Rankin Scale [mRS] 0-2) at 90 days. Secondary outcomes include the shift on the mRS score, neurological deterioration, symptomatic intracerebral haemorrhage and mortality. CONCLUSION: The HOPE trial will provide new information on the safety and efficacy of different BP targets following EVT according to the degree of final recanalization in patients with AIS.

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INTRODUCTION: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESS II) study. METHODS: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. RESULTS: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. CONCLUSION: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.

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[This corrects the article on p. 5994 in vol. 14, PMID: 38021143.].

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BACKGROUND AND OBJECTIVE: The limited availability of human bone samples for investigation leads to the demand for alternatives. Bone surrogates are crucial in promoting research on the intricate mechanics of osseous tissue. However, solutions are restricted to commercial brands, which frequently fail to faithfully replicate the mechanical response of bone, or oversimplified customised simulants designed for a specific application. The manufacturing and assessment of reliable bone surrogates made of polylactic acid via material extrusion-based additive manufacturing are presented in this work. METHODS: An experimental and numerical study with 3D-printed dog-bone and prismatic specimens was carried out to characterise the polymeric feedstock and analyse the influence of process parameters under three-point bending and quasi-static conditions. Besides, three porcine rib samples were considered as a reference for the development of the artificial bones. Bone surrogates were manufactured from the 3D-scanned real bone geometries. In order to reproduce the trabecular and cortical bone, a lattice structure for the infill and a compact shell surrounding the core were employed. Infill density and shell thickness were evaluated through different printing configurations. Additionally, a computational analysis based on the phase-field approach was conducted to simulate the experimental tests and predict fracture. The modelling considered homogenisation of the infill material. RESULTS: Outcomes demonstrated the potential of the presented methodology. Maximum force and flexural stiffness were compared to real bone properties to find the optimal printing configuration, replicating the flexural mechanical behaviour of bone tissue. Certain configurations accurately reproduce the studied properties. Regarding the numerical model, strength and stiffness prediction was validated with experimental results. CONCLUSIONS: The presented methodology enables the manufacturing of artificial bones with accurate geometries and tailored mechanical properties. Furthermore, the described modelling strategy offers a powerful tool for designing bone surrogates.

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The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

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PURPOSE: Cost containment and efficiency in the provision of health care are primary concerns for health systems that aim to provide affordable, high-quality care. Between 2005 and 2015, Seguro Poplar's Fund against Catastrophic Expenditures (FPGC) funded ALL treatment in Mexico. Before January 1, 2011, FPGC reimbursed a fixed amount per patient according to risk. In 2011, the per capita reimbursement method changed to fee for service. We used this natural experiment to estimate the impact of the reimbursement policy change on average expenditure and quality of care for ALL treatment in Mexico. METHODS: We used nationwide reimbursement data from the Seguro Poplar's FPGC from 2005 to 2015. We created a patient cohort to assess 3-year survival and estimate the average reimbursement before and after the fee-for-service policy. We examined survival and expenditure impacts, controlling for patients' and providers' characteristics, including sex, risk (standard and high), the volume of patients served, type of institution (federally funded v other), and level of care. To quantify the impact, we used a regression discontinuity approach. RESULTS: The average reimbursement for standard-risk patients in the 3-year survival cohort was $16,512 US dollars (USD; 95% CI, 16,042 to 17,032) before 2011 and $10,205 USD (95% CI, 4,659 to 12,541) under the fee-for-service reimbursement scheme after 2011. The average annual reimbursement per patient decreased by 136% among high-risk patients. The reduction was also significant for the standard-risk cohort, although the magnitude was substantially smaller (34%). CONCLUSION: As Mexico's government is currently restructuring the health system, our study provides evidence of the efficiency and effectiveness of the funding mechanism in the Mexican context. It also serves as a proof of concept for using administrative data to evaluate economic performance and quality of care of publicly funded health programs.

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Lignocellulosic biomass is widely available in the world. However, a consensus has yet to be established to evaluate the biomass valorization alternatives. The chemical composition is the primary technical limitation in selecting a transformation route to obtain value-added products. In this paper, the bagasse from non-centrifuged sugar (NCS) production and Pinus patula (PP) wood chips were analyzed in terms of complete chemical composition to establish their potential for selecting the transformation routes. A strategy to select the best route based on the chemical composition was applied and a feedstock criteria model was proposed. Schemes were obtained and compared using a bioprocess selection strategy proposed in previous works. As a result, the preliminary biorefinery schemes were finally defined. The assessment of schemes derived from the outlined strategy included technical, economic, environmental, and social analyses. The environmental evaluation was complemented with a geolocation assessment, revealing a 0.75-ton CO2-eq/yr contribution to the carbon footprint for local distribution. The sustainability index for the PP biorefinery and the bagasse from NCS production was analyzed, resulting in indices of 44.8 and 60.9, respectively. These values were primarily derived from the economic and environmental analyses of both processes.

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BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

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OBJECTIVE: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. METHODS: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. RESULTS: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. CONCLUSION: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

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The lifespan of an electrical transformer, primarily determined by the condition of its solid insulation, is well known under various operating conditions when mineral oil is the coolant in these machines. However, there is a trend toward replacing this oil with biodegradable fluids, especially esters; therefore, an understanding of the ageing of solid insulation with these fluids is essential. Currently available data do not allow for the selection of the best ester among those available on the market, as each study applies different conditions, making it impossible to compare results. Thus, this paper analyses the degradation of Kraft and Thermally Upgraded Kraft papers with the following five most promising commercial esters: sunflower, rapeseed, soybean, palm, and synthetic. The materials underwent accelerated thermal ageing at 130, 150, and 170 °C, and the integrity of the papers was evaluated through their polymerisation degree and the obtaining of the degradation kinetic models. The wide range of materials studied in this work, which were subjected to the same treatments, allows for a comparison of the esters, revealing significant differences in the impact of the alternative fluids. Sunflower, rapeseed, and soybean esters provided the best paper protection, i.e., the degree of polymerisation of Kraft paper in the tests at 150 °C decreased by 71% with these fluids, compared to the 83% reduction with mineral oil, 79% reduction with palm ester, and 75% reduction with synthetic ester. Furthermore, different kinetic models were obtained to predict the degradation; it was concluded that the Emsley model provides the best fit. Additionally, it was found that the behaviour of a dielectric fluid with one type of paper cannot be extrapolated, which is only noticeable in broad-scope studies.

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The objective of this work was to study the normal anatomy of the nasal cavity of the three species of big cats (leopard, lion, and cheetah) compared to the domestic cat through the use of computed tomography, magnetic resonance imaging, and rhinoscopy. Computed tomography allowed us to clearly visualize the entire bony and cartilaginous framework that supports the nasal cavity. Magnetic resonance imaging permitted better visualization of the soft tissues of this cavity. On the other hand, rhinoscopy enabled the direct visualization of the mucosa of the vestibule and nasal cavity, which is very useful in the diagnosis of masses or foreign bodies. Furthermore, with this technique, it has been possible to observe several small orifices from the nasolacrimal duct, the pharyngeal auditory tube, and the lateral nasal gland. Computed tomography, magnetic resonance imaging, and rhinoscopy are useful tools in analysis of the anatomical characteristics of the nasal cavity in these species.

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Large meteorite impacts release kinetic energy that induces rock deformation, high temperatures and fluid circulation during the cratering process. To understand the correlation between rock deformation and fluid circulation, it is relevant to investigate post-impact hydrothermal flux and its relation to the local geology. The Cerro do Jarau impact structure is a ~13.5 km diameter impact structure located in southern Brazil and formed on Cretaceous continental flood basalts of the Serra Geral Formation and underlying sedimentary strata. This study collected ground gamma-ray data over the structure and produced K, eTh and eU concentrations, eTh/K ratio and F-factor maps to characterize it in terms of its radiometric signatures and their respective spatial distribution. A general decrease in the concentration of the three elements was observed from the outer-rim towards the center of the crater. The central area is defined by very low radiometric values, with relatively high K values, thus indicating the occurrence of K-bearing rocks. Numerical simulations using the HYDROTHERM 3 code showed the fluid circulation pattern over the impact structure. Data interpretation resulted in a scenery consistent with potential fluid remobilization within the impact structure related to hydrothermal processes in the late stages of the crater formation process.

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PURPOSE: To compare the safety and efficacy of a 100 microgram subconjunctival injection of liposome-encapsulated sirolimus (SCJS) to cyclosporine (CsA) or tacrolimus (CsA/T) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. METHODS: Dogs with signs and symptoms of KCS were block-randomized to one of two treatment groups: Biweekly SCJS or conventional treatment (CsA/T). Schirmer tear test 1 (STT-1) scores, conjunctival hyperemia (CH) scores, corneal opacity (CO) scores, and clinical evaluation of potential side effects were recorded every 2 weeks for 14 weeks for both groups. Differences between groups were analyzed using the mixed results ANOVA and U-Mann Whitney tests (p < .05 was considered significant). RESULTS: A total of 30 eyes were included in the study, of which 20 eyes completed follow-up. There was no statistically significant interaction between the treatment group and time on STT-1 score (p = .165), and median CH and CO scores showed no statistically significant differences between groups (p = .353 and p = .393, respectively). There were no clinically significant side effects present in any subject at any time. CONCLUSION: In this trial, a 1 mg/mL (100 micrograms) SCJS every 2 weeks showed similar safety and efficacy profiles as daily CsA/T in dogs with KS after 14 weeks of treatment. Larger studies should be performed to further assess SCJS as an alternative treatment for KCS.

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INTRODUCTION: Aircraft cabins, susceptible to disease transmission, require effective strategies to minimize the spread of airborne diseases. This paper reviews the James Reason Swiss Cheese Theory in mitigating these risks, as implemented by the International Civil Aviation Organization during the COVID-19 pandemic. It also evaluates the use of airborne ultraviolet-C (UV-C) light as an additional protective measure.METHODS: Our approach involved a thorough literature review by experts and a detailed risk-vs.-benefit analysis. The review covered existing research to understand the scientific foundation, while the analysis used established techniques to assess the impact of influenza and COVID-19 in terms of infections, deaths, and economic costs.RESULTS: Integrating UV-C light in aircraft cabins, when applied with appropriate scientific understanding and engineering safeguards, has the potential to reduce in-flight disease transmission. This additional mitigation strategy can work synergistically with existing measures.DISCUSSION: The research and risk-vs.-benefit analysis present strong evidence for the safety and effectiveness of continuous UV-C disinfection in aircraft cabins. It suggests that UV-C light, maintained below exposure limits, can be a valuable addition to existing measures against disease transmission during flights.Belland K, Garcia D, DeJohn C, Allen GR, Mills WD, Glaudel SP. Safety and effectiveness assessment of ultraviolet-C disinfection in aircraft cabins. Aerosp Med Hum Perform. 2024; 95(3):147-157.

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