Efficacy and Safety of Pericapsular Nerve Group Block for Hip Fracture Surgery under Spinal Anesthesia: A Meta-Analysis.

Objective: To evaluate the effectiveness and safety of pericapsular nerve group (PENG) block for hip fracture surgery under spinal anesthesia. Methods: This meta-analysis was registered on INPLASY (INPLASY202270005). PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched to collect the randomized controlled trials of the PENG block applied to hip fracture surgery in the setting of spinal anesthesia, with the search period from inception to 1 May 2023. Two independent researchers gradually screened the literature, evaluated the quality, extracted the data, and eventually pooled data using RevMan 5.4. Results: Fifteen articles with 890 patients were enrolled. The combined results showed that the PENG block reduced pain scores during position placement (SMD = -0.35; 95% CI [-0.67, 0.02]; P=0.04; I2 = 0%). Subgroup analyses showed that compared to the unblocked group, the PENG block reduced pain scores at 12 h, 24 h, and 48 h postoperatively. The incidence of postoperative hypokinesia was reduced (RR = 0.11; 95% CI [0.01, 0.86]; P=0.04; I2 = 0.00%). The time to first walking was advanced (SMD = -0.90; 95% CI [-1.17, 0.63]; P < 0.00001; I2 = 0%). Conclusion: The PENG block can reduce postoperative pain and pain during spinal anesthesia positioning, which is helpful to improve the operability and comfort of spinal anesthesia and facilitate postoperative muscle strength recovery and early activity.

The Effect of Scalp Nerve Block on Postoperative Analgesia and Stress Response in Patients Undergoing Craniotomy: A Meta-Analysis.

Objective: To evaluate the effect of scalp nerve block (SNB) on postoperative analgesia and stress response in patients undergoing craniotomy by meta-analysis. Methods: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials involving SNB for elective craniotomy under general anesthesia from inception to August 1, 2022. Meta-analysis was performed using RevMan 5.4 and Stata MP17.0. Based on scalp block operation time (preoperative block, postoperative block), different control groups (no block, normal saline), local anesthetic types (bupivacaine, levobupivacaine, ropivacaine), the postoperative pain score at different time points was analyzed by subgroup analysis. Results: 23 studies involving 1515 patients were included. The combined results showed that SNB could significantly reduce the pain scores at all time points compared with the control group (P < .05). Subgroup analysis showed that the analgesic effect of preoperative scalp nerve block was better than that of postoperative block, and the effect of ropivacaine and levobupivacaine was better than bupivacaine. SNB could reduce morphine consumption within 48 hours after surgery (SMD = -1.51, 95% CI -2.80 -0.21, P = .02, I2 = 89%). The first rescue analgesia time was significantly longer in the SNB group than the control group (SMD = 0.57, 95% CI 0.16-0.99, P = .01, I2 = 68.76%). Compared with the control group, the levels of postoperative angiotensin, intraoperative blood glucose, and both intraoperative and postoperative cortisol levels were significantly decreased (P < .05). SNB can inhibit hemodynamic changes caused by surgical stimulation and effectively reduce the incidence of postoperative nausea and vomiting (RR = 0.71, 95% CI 0.51~0.97, P = .03). Conclusion: Scalp nerve block is an effective analgesic that reduces pain within 48 hours after craniotomy. It effectively inhibit the stress response caused by surgical stimulation, stabilize hemodynamics, and reduce the incidence of postoperative nausea and vomiting.

Field investigation combined with modeling uncovers the ecological heterogeneity of Aedes albopictus habitats for strategically improving systematic management during urbanization.

BACKGROUND: Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. METHODS: A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015-2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. RESULTS: A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. CONCLUSIONS: Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management.

Mechanically sensitive HSF1 is a key regulator of left-right symmetry breaking in zebrafish embryos.

The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.

Long-circulation zwitterionic dendrimer nanodrugs for phototherapy of tumors.

The development of stealth and effective antitumor nanodrugs has been drawing great attention. Herein, generation five poly(amide amine) dendrimer (G5 PAMAM) was modified by zwitterionic material carboxybetaine methacrylamide (CBMAA) on its surface to prepare zwitterionic dendrimer (G5-CBMAAn). The results showed that G5-CBMAA30 had the longest blood circulation time due to its thickest zwitterionic layer, and its residual rate after injection into mice at 2 and 12 h was as high as 47.22 % and 14.37 %, respectively. Nanodrug G5-CBMAA30-ICG was prepared by containing indocyanine green (ICG) in the cavity of G5-CBMAA30. G5-CBMAA30-ICG had better tumor targeting ability and antitumor effect than free ICG in mice after laser irradiation, and the tumor inhibition rate was 96.6 % after 14 days' treatment. The prepared G5-CBMAA30-ICG has great potential applications in the field of antitumor by phototherapy.

Self-Organization of Tissue Growth by Interfacial Mechanical Interactions in Multilayered Systems.

Morphogenesis is a spatially and temporally regulated process involved in various physiological and pathological transformations. In addition to the associated biochemical factors, the physical regulation of morphogenesis has attracted increasing attention. However, the driving force of morphogenesis initiation remains elusive. Here, it is shown that during the growth of multilayered tissues, a morphogenetic process can be self-organized by the progression of compression gradient stemmed from the interfacial mechanical interactions between layers. In tissues with low fluidity, the compression gradient is progressively strengthened during growth and induces stratification by triggering symmetric-to-asymmetric cell division reorientation at the critical tissue size. In tissues with high fluidity, compression gradient is dynamic and induces cell rearrangement leading to 2D in-plane morphogenesis instead of 3D deformation. Morphogenesis can be tuned by manipulating tissue fluidity, cell adhesion forces, and mechanical properties to influence the progression of compression gradient during the development of cultured cell sheets and chicken embryos. Together, the dynamics of compression gradient arising from interfacial mechanical interaction provides a conserved mechanism underlying morphogenesis initiation and size control during tissue growth.

Polyethyleneimine-Oleic Acid Micelles-Stabilized Palladium Nanoparticles as Highly Efficient Catalyst to Treat Pollutants with Enhanced Performance.

Water soluble organic molecular pollution endangers human life and health. It becomes necessary to develop highly stable noble metal nanoparticles without aggregation in solution to improve their catalytic performance in treating pollution. Polyethyleneimine (PEI)-based stable micelles have the potential to stabilize noble metal nanoparticles due to the positive charge of PEI. In this study, we synthesized the amphiphilic PEI-oleic acid molecule by acylation reaction. Amphiphilic PEI-oleic acid assembled into stable PEI-oleic acid micelles with a hydrodynamic diameter of about 196 nm and a zeta potential of about 34 mV. The PEI-oleic acid micelles-stabilized palladium nanoparticles (PO-PdNPsn) were prepared by the reduction of sodium tetrachloropalladate using NaBH4 and the palladium nanoparticles (PdNPs) were anchored in the hydrophilic layer of the micelles. The prepared PO-PdNPsn had a small size for PdNPs and good stability in solution. Noteworthily, PO-PdNPs150 had the highest catalytic activity in reducing 4-nitrophenol (4-NP) (Knor = 18.53 s-1mM-1) and oxidizing morin (Knor = 143.57 s-1M-1) in aqueous solution than other previous catalysts. The enhanced property was attributed to the improving the stability of PdNPs by PEI-oleic acid micelles. The method described in this report has great potential to prepare many kinds of stable noble metal nanoparticles for treating aqueous pollution.

A versatile nanoplatform based on multivariate porphyrinic metal-organic frameworks for catalytic cascade-enhanced photodynamic therapy.

In recent years, the antitumor application of photodynamic therapy (PDT) has gained widespread interest in treating solid tumors. Due to the hypoxic environment in tumors, the major limit of PDT seems to be the source of oxygen. In this work, we attempted to relieve hypoxia and enhance photodynamic therapy, and therefore, designed and assembled a catalytic cascade-enhanced PDT multifunctional nanoplatform. The mentioned platform termed UIO@Ca-Pt is based on porphyrinic metal-organic framework (UIO) combination, which is simultaneously loaded by CaO2 NPs with polydopamine (PDA) and then the Pt raw material to further improve biocompatibility and efficiency. In a tumor microenvironment, CaO2 could react with water to generate calcium hydroxide and hydrogen peroxide, which was further decomposed by Pt nanoparticles to form oxygen, thereby facilitating the generation of cytotoxic singlet oxygen by photosensitizer TCPP under laser irradiation. Both in vitro and in vivo experiment results confirmed the excellent oxygen production capacity and enhanced PDT effect of UIO@Ca-Pt. With guaranteed safety in PDT, the oxygen-supplying strategy might stimulate considerable interest in the development of various metal-organic materials with multifunctionality for tumor diagnosis and therapy.

"Stealth" dendrimers with encapsulation of indocyanine green for photothermal and photodynamic therapy of cancer.

Poly(amido amine) dendrimers and indocyanine green have inevitable interaction with proteins and cells, which induces biological toxicity and reduces therapeutic efficacy in vivo. To overcome these shortcomings, a new drug delivery system G5MEK7C(n)-ICG with a "stealth" layer was prepared. The surface of G5MEK7C(n)-ICG was modified with double-layer super hydrophilic zwitterionic materials. In the "stealth" double-layer structure, the outer layer was consisted of zwitterionic Glu-Lys-Glu-Lys-Glu-Lys-Cys (EK7) peptide, and the inner layer was composed of amino and carboxyl groups with a ratio of 1:1. DLS results showed that the average hydrodynamic size of G5MEK7C(n)-ICG was about 25-30 nm, and the zeta potential was proven to undergo a slight charge reversal with the increasing pH values of solutions. Furthermore, G5MEK7C(n)-ICG exhibited excellent biocompatibility to red blood cells and proteins resistance. Photothermal and photodynamic experiments demonstrated that G5MEK7C(n)-ICG had a good photothermal conversion effect and generated singlet oxygen (1O2) under laser irradiation. The MTT and hemolysis results showed that the toxicity of G5 PAMAM was significantly reduced after modification double-layer structure. Cytotoxicity studies and flow cytometry showed G5MEK7C(70)-ICG under laser irradiation had a good effect on killing A549 cells. More importantly, the tumor inhibition rate of mice treated with G5MEK7C(70)-ICG (under laser irradiation) was 78.2% in vivo, which was higher than that of mice treated with free ICG. Compared with free ICG, G5MEK7C(70)-ICG caused less damage to the liver according to the enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Therefore, dendrimers modified with a zwitterionic double layer will be a promising candidate as a drug delivery system.

Projecting Long-term Health and Economic Burden of COPD in the United States.

BACKGROUND: In the United States, COPD is a leading cause of mortality, with a substantial societal health and economic burden. With anticipated population growth, it is important for various stakeholders to have an estimate for the projected burden of disease. RESEARCH QUESTION: The goal of this study was to model the 20-year health and economic burden of COPD, from 2019 to 2038, in the United States. STUDY DESIGN AND METHODS: Using country-specific data from published literature and publicly available datasets, a dynamic open cohort Markov model was developed in a probabilistic Monte Carlo simulation. Population growth was modeled across different subgroups of age, sex, and smoking. The COPD prevalence rates were calibrated for different subgroups, and distributions of severity grades were modeled based on smoking status. Direct costs, indirect absenteeism costs, losses of quality-adjusted life years (QALYs), and number of exacerbations and deaths associated with COPD were projected. RESULTS: The 20-year discounted direct medical costs attributable to COPD were estimated to be $800.90 billion (95% credible interval [CrI], 565.29 billion-1,081.29 billion), with an expected $337.13 billion in male subjects and $463.77 billion in female subjects. The 20-year discounted indirect absenteeism costs were projected to be $101.30 billion (70.82 billion-137.41 billion). The 20-year losses of QALYs, number of exacerbations, and number of deaths associated with COPD were 45.38 million (8.63 million-112.07 million), 315.08 million (228.59 million-425.33 million), and 9.42 million (8.93 million-9.93 million), respectively. The proportion of disease burden attributable to continued smoking was 34% in direct medical costs, 35% in indirect absenteeism costs, and 37% in losses of QALYs over 20 years. INTERPRETATION: This study projects the substantial burden of COPD that the American society is expected to incur with current patterns for treatments and smoking rates. Mitigating such burden requires targeted budget appropriations and cost-effective interventions.

Introducing ortho-methoxyl group as a fluorescence-enhancing and bathochromic-shift bi-functional strategy for typical cysteine sensors.

A practical strategy of introducing ortho-methoxyl group was explored to achieve the fluorescence-enhancing and bathochromic-shift bi-functional optimization. It was tested in the Cys sensing ISOPH-X series, thus the successful case, ISOPH-2, was obtained. It realized the optimization in a simple and compatible way. The corresponding strategy was basically established during the confirmation of checkpoints including applicable steadiness (over 24 h), wide pH range (7.0-9.0), rapid response (20 min), good biocompatibility, high sensitivity (LOD = 0.072 nm), high selectivity and biological monitoring of Cys in living cells as well as C. elegans. In this work, the o-methoxyl introduction strategy led to a 15 nm red shift and a near 4-fold fluorescence enhancement. This strategy could be combined with the double bond-introducing approach. Compared with reported strategies, by breaking the dilemma between red shift and strong fluorescent intensity, this strategy might offer beneficial information for exploiting better sensors with more fluorophores and mechanisms for their targets.

Oxygen Self-Sufficient Core-Shell Metal-Organic Framework-Based Smart Nanoplatform for Enhanced Synergistic Chemotherapy and Photodynamic Therapy.

The abnormal angiogenesis and insufficient oxygen supply in solid tumors lead to intratumoral hypoxia, which severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a multifunctional nanoplatform (ZDZP@PP) based on a zeolitic imidazolate framework-67 (ZIF-67) core as a hydrogen peroxide catalyst, a zeolitic imidazolate framework-8 (ZIF-8) shell with a pH-responsive property, and a polydopamine-poly(ethylene glycol) (PDA-PEG) layer for improving the biocompatibility is fabricated for not only relieving tumor hypoxia but also enhancing the efficacy of combination chemo-photodynamic therapy. The chemotherapy drug doxorubicin (DOX) and photosensitizer protoporphyrin IX (PpIX) are encapsulated in different layers independently; thus, a unique two-stage stepwise release becomes possible. Moreover, the nanoplatform can effectively decompose hydrogen peroxide to produce oxygen and thus relieve tumor hypoxia, which further facilitates the production of cytotoxic reactive oxygen species (ROS) by PpIX under laser irradiation. Both in vitro and in vivo experimental results confirm that the combination chemo-photodynamic therapy with the ZDZP@PP nanoplatform can provide more effective cancer treatment than chemotherapy or PDT alone. Consequently, the oxygen self-sufficient multifunctional nanoplatform holds promising potential to overcome hypoxia and treat solid tumors in the future.

Discovery of novel pyrazoline derivatives containing methyl-1H-indole moiety as potential inhibitors for blocking APC-Asef interactions.

A series of novel pyrazoline derivatives containing methyl-1H-indole moiety were discovered as potential inhibitors for blocking APC-Asef interactions. The top hit Q19 suggested potency of inhibiting APC-Asef interactions and attractive preference for human-sourced colorectal cells. It was already comparable with the previous representative and the positive control Regorafenib before further pharmacokinetic optimization. The introduction of methyl-1H-indole moiety realized the Mitochondrial affection thus might connect the impact on the protein-interaction level with the apoptosis events. The molecular docking simulation inferred that bringing trifluoromethyl groups seemed a promising approach for causing more key interactions such as H-bonds. This work raised referable information for further discovery of inhibitors for blocking APC-Asef interactions.

Robust optimal predictive control of heavy haul train under imperfect communication.

With the rapid developments in communication technology, the bidirectional wireless communication channel is widely used to exchange information between the train and wayside control center. As an emerging technology, the communication based heavy haul train control (CBHHTC) system is becoming a better alternative for administrative department to provide the greater transport capacity. In order to put the latest automatic control methods into the practice, this paper investigates the robust optimal control problem of heavy haul train under CBHHTC. By formulating the CBHHTC based real-time control procedure as a networked control system (NCS) model, the possible data loss phenomenon in the wireless communications is considered, and its impact on the stability and performances of the controller design is elaborated. On the basis of Lyapunov stability theory and model predictive control (MPC) approach, a set of linear matrix inequalities (LMIs) is given as sufficient conditions to ensure the velocity tracking ability, energy-efficiency and operational safety with a prescribed H∞ disturbance attenuation level under the control constraints. Case studies are conducted to illustrate the effectiveness of the proposed controller.

Optimising the cost-effectiveness of speed limit enforcement cameras.

BACKGROUND: Using the 140 speed cameras in New York City (NYC) as a case study, we explore how to optimise the number of cameras such that the most lives can be saved at the lowest cost. METHODS: A Markov model was built to explore the economic and health impacts of speed camera installations in NYC as well as the optimal number and placement. Both direct and indirect medical savings associated with speed cameras are weighed against their cost. Health outcomes are measured in terms of quality-adjusted life years (QALYs). RESULTS: Over the lifetime of an average NYC resident, the existing 140 speed cameras increase QALYs by 0.00044 units (95% credible interval (CrI) 0.00027 to 0.00073) and reduce costs by US$70 (95% CrI US$21 to US$131) compared with no speed cameras. The return on investment would be maximised where the number of cameras more than doubled to 300. This would further increase QALY gains per resident by 0.00083 units (95% CrI 0.00072 to 0.00096) while reducing medical costs by US$147 (95% CrI US$70 to US$221) compared with existing speed cameras. Overall, this increase in cameras would save 7000 QALYs and US$1.2 billion over the lifetime of the current cohort of New Yorkers. CONCLUSION: Speed cameras rank among the most cost-effective social policies, saving both money and lives.

Subjective assessments of income and social class on health and survival: An enigma.

We examined the association between various measures of subjective social class identification (SSCI) and self-rated health as well as survival using the 2014 General Social Survey-National Death Index dataset (n = 21,108). We used multinomial logistic regression models to assess the association between SSCI and self-rated health and used Cox proportional hazards to assess the association between SSCI and survival. All analyses were adjusted for age, year at interview, race, gender, family income, and educational attainment level. The measures of SSCI that we had available were strongly correlated with self-rated health after controlling for objective measures of social status. For example, those who saw themselves as lower class were nine times as likely to self-report poor rather than excellent health status (odds ratio = 8.69; 95% confidence interval = 5.04-14.98) compared with those saw themselves as upper class. However, no such associations were observed for survival. While our alternative measures of SSCI were important predictors of self-rated health, they were not predictive of survival. This suggests that there may be potential confounding between two perceptions: SSCI and self-rated health.

Photoperiodic diapause in a subtropical population of Aedes albopictus in Guangzhou, China: optimized field-laboratory-based study and statistical models for comprehensive characterization.

BACKGROUND: Aedes albopictus is among the 100 most invasive species worldwide and poses a major risk to public health. Photoperiodic diapause provides a crucial ecological basis for the adaptation of this species to adverse environments. Ae. albopictus is the vital vector transmitting dengue virus in Guangzhou, but its diapause activities herein remain obscure. METHODS: In the laboratory, yeast powder and food slurry were compared for a proper diapause determination method, and the critical photoperiod (CPP) was tested at illumination times of 11, 11.5, 12, 12.5, 13, and 13.5 h. A 4-parameter logistic (4PL) regression model was selected to estimate the CPP. In the field, the seasonal dynamics of the Ae. albopictus population, egg diapause, and hatching of overwintering eggs were investigated monthly, weekly, and daily, respectively. A distributed lag non-linear model (DLNM) was used to assess the associations of diapause with meteorological factors. RESULTS: In the laboratory, both the wild population and the Foshan strain of Ae. albopictus were induced to diapause at an incidence greater than 80%, and no significant difference (P > 0.1) was observed between the two methods for identifying diapause. The CPP of this population was estimated to be 12.312 h of light. In the field, all of the indexes of the wild population were at the lowest levels from December to February, and the Route Index was the first to increase in March. Diapause incidence displayed pronounced seasonal dynamics. It was estimated that the day lengths of 12.111 h at week2016, 43 and 12.373 h at week2017, 41 contributed to diapause in 50% of the eggs. Day length was estimated to be the main meteorological factor related to diapause. CONCLUSIONS: Photoperiodic diapause of Ae. albopictus in Guangzhou of China was confirmed and comprehensively elucidated in both the laboratory and the field. Diapause eggs are the main form for overwintering and begin to hatch in large quantities in March in Guangzhou. Furthermore, this study also established an optimized investigation system and statistical models for the study of Ae. albopictus diapause. These findings will contribute to the prevention and control of Ae. albopictus and mosquito-borne diseases.

The Trade-Off between Optimizing Flight Patterns and Human Health: A Case Study of Aircraft Noise in Queens, NY, USA.

Objectives: Airports in the U.S. have gradually been transitioning to automated flight systems. These systems generate new flight paths over populated areas. While they can improve flight efficiency, the increased noise associated with these novel flight patterns potentially pose serious health threats to the overflown communities. In this case study, we estimated the monetary benefits relative to health losses associated with one significant change in flight patterns at LaGuardia Airport, year-round use of "TNNIS Climb", which happened in 2012 as a result of flight automation in New York City. Prior to that, the use of the TNNIS Climb was limited to the U.S. Open tennis matches. Methods: We developed a decision-analytic model using Markov health states to compare the costs and quality-adjusted life years (QALYs) gained associated with the limited use of TNNIS (old status quo) and the year-round use of TNNIS (current status quo). The TNNIS Climb increases airplane noise to above 60 decibels (dB) over some of the most densely populated areas of the city. We used this increased exposure to noise as the basis for estimating ground-level health using data from sound monitors. The total costs (including both direct and indirect costs), QALYs, and the incremental cost-effectiveness ratio (ICER) were estimated for the limited versus the year-round use of the TNNIS Climb. Results: The incremental lifetime costs and QALYs per person exposed to noise associated with the limited versus the year-round use of TNNIS was $11,288, and 1.13, respectively. Therefore, the limited use of TNNIS had an ICER of $10,006/QALY gained relative to the year-round of TNNIS. Our analyses were robust to changes in assumptions and data inputs. Conclusions: Despite increases in efficiency, flight automation systems without a careful assessment of noise might generate flight paths over densely populated areas and cause serious health conditions for the overflown communities.