The syncope core management process in the emergency department: a consensus statement of the EUSEM syncope group.

The European Society of Cardiology issued updated syncope guidelines in 2018 which included recommendations for managing syncope in the emergency department (ED) setting. However, these guidelines lack detailed process-oriented instructions regarding the fact that ED syncope patients initially present with a transient loss of consciousness (TLOC), which can have a broad spectrum of causes. This study aims to establish a European consensus on the general process of the workup and care for patients with suspected syncope and provides rules for sufficient and systematic management of the broad group of syncope (initially presenting as TLOC) patients in the ED. A variety of European diagnostic and therapeutic standards for syncope patients were reviewed and summarized in three rounds of a modified Delphi process by the European Society for Emergency Medicine syncope group. Based on a consensus statement, a detailed process pathway is created. The primary outcome of this work is the presentation of a universal process pathway for the structured management of syncope patients in European EDs. The here presented extended event process chain (eEPC) summarizes and homogenizes the process management of European ED syncope patients. Additionally, an exemplary translation of the eEPC into a practice-based flowchart algorithm, which can be used as an example for practical use in the ED, is provided in this work. Syncope patients, initially presenting with TLOC, are common and pose challenges in the ED. Despite variations in process management across Europe, the development of a universally applicable syncope eEPC in the ED was successfully achieved. Key features of the consensus and eEPC include ruling out life-threatening causes, distinguishing syncope from nonsyncopal TLOCs, employing syncope risk stratification categories and based on this, making informed decisions regarding admission or discharge.

Diagnosis and management of acute aortic dissection in the emergency department.

Acute aortic dissection is often misdiagnosed as a result of its atypical presentations. It affects 4000 patients a year in the UK of all ages, not just older patients, with increasing numbers of cases expected in the future because of the ageing population. Dissection of the aortic wall leads to sudden, severe pain, and commonly end-organ symptoms which must be recognised. Acute aortic dissection can be challenging to diagnose in the emergency department because of the multitude of possible presentations and the need for selective testing with Computed Tomography Angiography (CTA). Clinicians often miss acute aortic dissection because it is not considered in the differential diagnosis, and the challenge lies in identifying acute aortic dissection in a sea of complaints of chest, back and abdominal pain. There are several ways to improve diagnosis, including awareness campaigns, better education about patients in which to consider acute aortic dissection, and improved detection strategies including which patients should receive CTA. Clinical decision tools and biomarkers could help, but further research is required and is a research focus in emergency medicine. Once diagnosed, blood pressure control, analgesia and urgent surgery or transfer to enable this to occur with minimal delay is required.

Efficient Model-Based Anthropometry under Clothing Using Low-Cost Depth Sensors.

Measuring human body dimensions is critical for many engineering and product design domains. Nonetheless, acquiring body dimension data for populations using typical anthropometric methods poses challenges due to the time-consuming nature of manual methods. The measurement process for three-dimensional (3D) whole-body scanning can be much faster, but 3D scanning typically requires subjects to change into tight-fitting clothing, which increases time and cost and introduces privacy concerns. To address these and other issues in current anthropometry techniques, a measurement system was developed based on portable, low-cost depth cameras. Point-cloud data from the sensors are fit using a model-based method, Inscribed Fitting, which finds the most likely body shape in the statistical body shape space and providing accurate estimates of body characteristics. To evaluate the system, 144 young adults were measured manually and with two levels of military ensembles using the system. The results showed that the prediction accuracy for the clothed scans remained at a similar level to the accuracy for the minimally clad scans. This approach will enable rapid measurement of clothed populations with reduced time compared to manual and typical scan-based methods.

Diagnosis of Acute Aortic Syndrome in the Emergency Department (DAShED) study: an observational cohort study of people attending the emergency department with symptoms consistent with acute aortic syndrome.

BACKGROUND: The diagnosis of acute aortic syndrome (AAS) is commonly delayed or missed in the ED. We describe characteristics of ED attendances with symptoms potentially associated with AAS, diagnostic performance of clinical decision tools (CDTs) and physicians and yield of CT aorta angiogram (CTA). METHODS: This was a multicentre observational cohort study of adults attending 27 UK EDs between 26 September 2022 and 30 November 2022, with potential AAS symptoms: chest, back or abdominal pain, syncope or symptoms related to malperfusion. Patients were preferably identified prospectively, but retrospective recruitment was also permitted. Anonymised, routinely collected patient data including components of CDTs, was abstracted. Clinicians treating prospectively identified patients were asked to record their perceived likelihood of AAS, prior to any confirmatory testing. Reference standard was radiological or operative confirmation of AAS. 30-day electronic patient record follow-up evaluated whether a subsequent diagnosis of AAS had been made and mortality. RESULTS: 5548 patients presented, with a median age of 55 years (IQR 37-72; n=5539). 14 (0.3%; n=5353) had confirmed AAS. 10/1046 (1.0%) patients in whom the ED clinician thought AAS was possible had AAS. 5/147 (3.4%) patients in whom AAS was considered the most likely diagnosis had AAS. 2/3319 (0.06%) patients in whom AAS was considered not possible did have AAS. 540 (10%; n=5446) patients underwent CT, of which 407 were CTA (7%). 30-day follow-up did not reveal any missed AAS diagnoses. AUROC (area under the receiver operating characteristic) curve for ED clinician AAS likelihood rating was 0.958 (95% CI 0.933 to 0.983, n=4006) and for individual CDTs were: Aortic Dissection Detection Risk Score (ADD-RS) 0.674 (95% CI 0.508 to 0.839, n=4989), AORTAs 0.689 (95% CI 0.527 to 0.852, n=5132), Canadian 0.818 (95% CI 0.686 to 0.951, n=5180) and Sheffield 0.628 (95% CI 0.467 to 0.788, n=5092). CONCLUSION: Only 0.3% of patients presenting with potential AAS symptoms had AAS but 7% underwent CTA. CDTs incorporating clinician gestalt appear to be most promising, but further prospective work is needed, including evaluation of the role of D-dimer. TRIAL REGISTRATION NUMBER: NCT05582967; NCT05582967.

Management of syncope in the Emergency Department: a European prospective cohort study (SEED).

BACKGROUND AND IMPORTANCE: In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe. OBJECTIVES: To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope). DESIGN: Prospective, multicentre, observational cohort study. SETTINGS AND PARTICIPANTS: Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin. MAIN RESULTS: Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3-88.9%), use of an observation/decision unit (0-100%), and percentage high-risk (64.8-88.9%) varies widely between countries. CONCLUSION: This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.

Assessment of open-field fluorescence guided surgery systems: implementing a standardized method for characterization and comparison.

Significance: Fluorescence guided surgery (FGS) has demonstrated improvements in decision making and patient outcomes for a wide range of surgical procedures. Not only can FGS systems provide a higher level of structural perfusion accuracy in tissue reconstruction cases but they can also serve for real-time functional characterization. Multiple FGS devices have been Food and Drug administration (FDA) cleared for use in open and laparoscopic surgery. Despite the rapid growth of the field, there has been a lack standardization methods. Aim: This work overviews commonalities inherent to optical imaging methods that can be exploited to produce such a standardization procedure. Furthermore, a system evaluation pipeline is proposed and executed through the use of photo-stable indocyanine green fluorescence phantoms. Five different FDA-approved open-field FGS systems are used and evaluated with the proposed method. Approach: The proposed pipeline encompasses the following characterization: (1) imaging spatial resolution and sharpness, (2) sensitivity and linearity, (3) imaging depth into tissue, (4) imaging system DOF, (5) uniformity of illumination, (6) spatial distortion, (7) signal to background ratio, (8) excitation bands, and (9) illumination wavelength and power. Results: The results highlight how such a standardization approach can be successfully implemented for inter-system comparisons as well as how to better understand essential features within each FGS setup. Conclusions: Despite clinical use being the end goal, a robust yet simple standardization pipeline before clinical trials, such as the one presented herein, should benefit regulatory agencies, manufacturers, and end-users to better assess basic performance and improvements to be made in next generation FGS systems.

Review of optical reporters of radiation effects in vivo: tools to quantify improvements in radiation delivery technique.

Significance: Radiation damage studies are used to optimize radiotherapy treatment techniques. Although biological indicators of damage are the best assays of effect, they are highly variable due to biological heterogeneity. The free radical radiochemistry can be assayed with optical reporters, allowing for high precision titration of techniques. Aim: We examine the optical reporters of radiochemistry to highlight those with the best potential for translational use in vivo, as surrogates for biological damage assays, to inform on mechanisms. Approach: A survey of the radical chemistry effects from reactive oxygen species (ROS) and oxygen itself was completed to link to DNA or biological damage. Optical reporters of ROS include fluorescent, phosphorescent, and bioluminescent molecules that have a variety of activation pathways, and each was reviewed for its in vivo translation potential. Results: There are molecular reporters of ROS having potential to report within living systems, including derivatives of luminol, 2'7'-dichlorofluorescein diacetate, Amplex Red, and fluorescein. None have unique specificity to singular ROS species. Macromolecular engineered reporters unique to specific ROS are emerging. The ability to directly measure oxygen via reporters, such as Oxyphor and protoporphyrin IX, is an opportunity to quantify the consumption of oxygen during ROS generation, and this translates from in vitro to in vivo use. Emerging techniques, such as ion particle beams, spatial fractionation, and ultra-high dose rate FLASH radiotherapy, provide the motivation for these studies. Conclusions: In vivo optical reporters of radiochemistry are quantitatively useful for comparing radiotherapy techniques, although their use comes at the cost of the unknown connection to the mechanisms of radiobiological damage. Still their lower measurement uncertainty, compared with biological response assay, makes them an invaluable tool. Linkage to DNA damage and biological damage is needed, and measures such as oxygen consumption serve as useful surrogate measures that translate to in vivo use.

Child occupant safety in unconventional seating for vehicles with automated driving systems.

The objective of this study was to use computational models to study how unconventional seating positions and orientations in vehicles with Automated Driving System (ADS) may affect occupant response metrics of children with various restraint conditions. A literature review was first conducted to frame a simulation plan, including selections of surrogate ADS-equipped vehicles, potential seating arrangements, impact scenarios, anthropomorphic test device (ATD) models, and child restraint system (CRS) models that are relevant to the selected ATD models. Due to the lack of impact tests with child ATDs and CRS in farside, oblique, and rear impacts, 17 sled tests were conducted with CRS harness-restrained ATDs and vehicle belt-restrained ATDs in frontal, farside, oblique, and rear impact conditions. The sled tests were then used to validate a set of MADYMO (MAthematical DYnamic MOdels) v7.7 models. A total of 550 simulations were then conducted with four child ATDs and various CRS conditions across a range of conventional and unconventional seating locations and orientations under five impact directions. We did not find major safety concerns with ATDs restrained by harnessed CRSs based on the nature of ATD contacts. Compared with frontal and rear impacts, CRSs may rotate laterally in farside and oblique impacts, which could result in higher head and chest injury measures than frontal due to inertial loading to the CRS, and the larger lateral rotation of the CRS may lead to a contact between the CRS and vehicle interior. The major safety concern for vehicle belt-restrained ATDs (with and without booster) is that they have the potential to contact the seat next to them or the instrument panel behind them in a farside or oblique impact. Unconventional seating does not necessarily create additional safety concerns beyond what we know with the conventional seating. However, due to the orientation of the unconventional seats, the occupants on those seats may be involved in a higher percentage of oblique and rear-oblique impacts relative to their seating orientations than conventional seats, which may be considered in the future safety design process. This is the first study using different child ATDs and CRSs to investigate child occupant responses in a wide range of impact directions and seating orientations. Results from the sled tests and simulations provide a better understanding of child occupant responses in those crash conditions, but also identified several limitations of using frontal ATDs in other crash directions.

Mapping estimates of vascular permeability with a clinical indocyanine green fluorescence imaging system in experimental pancreatic adenocarcinoma tumors.

Significance: Pancreatic cancer tumors are known to be avascular, but their neovascular capillaries are still chaotic leaky vessels. Capillary permeability could have significant value for therapy assessment, and its quantification might be possible with macroscopic imaging of indocyanine green (ICG) kinetics in tissue. Aim: The capacity of using standard fluorescence surgical systems for ICG kinetic imaging as a probe for capillary leakage was evaluated using a clinical surgical fluorescence imaging system, as interpreted through vascular permeability modeling. Approach: Xenograft pancreatic adenocarcinoma models were imaged in mice during bolus injection of ICG to capture the kinetics of uptake. Image analysis included ratiometric data, normalization, and match to theoretical modeling. Kinetic data were converted into the extraction fraction of the capillary leakage. Results: Pancreatic tumors were usually less fluorescent than the surrounding healthy tissues, but still the rate of tumor perfusion could be assessed to quantify capillary extraction. Model simulations showed that flow kinetics stabilized after about 1 min beyond the initial bolus injection and that the relative extraction fraction model estimates matched the experimental data of normalized uptake within the tissue. The kinetics in the time period of 1 to 2 min post-injection provided optimal differential data between AsPC1 and BxPC3 tumors, although high individual variation exists between tumors. Conclusions: ICG kinetic imaging during the initial leakage phase was diagnostic for quantitative vascular permeability within pancreatic tumors. Methods for autogain correction and normalized model-based interpretation allowed for quantification of extraction fraction and difference identification between tumor types in early timepoints.

Longitudinal Degradation of Pavement Marking Detectability for Mobile LiDAR Sensing Technology in Real-World Use.

Recent advancements in vehicle automation and driver-assistance systems that detect pavement markings has increased the importance of the detectability of pavement markings through various sensor modalities across weather and road conditions. Among the sensing techniques, light detection and ranging (LiDAR) sensors have become popular for vehicle-automation applications. This study used low-cost mobile multi-beam LiDAR to assess the performance of several types of pavement marking materials installed on a limited-access highway in various conditions, and quantified the degradation in detection performance over three years. Four marking materials, HPS-8, polyurea, cold plastic, and sprayable thermoplastic, were analyzed in the current study. LiDAR reflectivity data extracted from a total of 210 passes through the test sections were analyzed. A new detectability score based on LiDAR intensity data was proposed to quantify the marking detectability. The results showed that the pavement marking detectability varied across the material types over the years. The results provide guidance for selecting materials and developing maintenance schedules when marking detectability by LiDAR is a concern.

Efficacy of the combination of monoclonal antibodies against the SARS-CoV-2 Beta and Delta variants.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest healthcare issue worldwide. This study aimed to develop a monoclonal antibody against SARS-CoV-2 from B cells of recovered COVID-19 patients, which might have beneficial therapeutic purposes for COVID-19 patients. We successfully generated human monoclonal antibodies (hmAbs) against the receptor binding domain (RBD) protein of SARS-CoV-2 using developed hybridoma technology. The isolated hmAbs against the RBD protein (wild-type) showed high binding activity and neutralized the interaction between the RBD and the cellular receptor angiotensin-converting enzyme 2 (ACE2) protein. Epitope binning and crystallography results displayed target epitopes of these antibodies in distinct regions beneficial in the mix as a cocktail. The 3D2 binds to conserved epitopes among multi-variants. Pseudovirion-based neutralization results revealed that the antibody cocktail, 1D1 and 3D2, showed high potency in multiple variants of SARS-CoV-2 infection. In vivo studies showed the ability of the antibody cocktail treatment (intraperitoneal (i.p.) administration) to reduce viral load (Beta variant) in blood and various tissues. While the antibody cocktail treatment (intranasal (i.n.) administration) could not significantly reduce the viral load in nasal turbinate and lung tissue, it could reduce the viral load in blood, kidney, and brain tissue. These findings revealed that the efficacy of the antibody cocktail, 1D1 and 3D2, should be further studied in animal models in terms of timing of administration, optimal dose, and efficacy to mitigate inflammation in targeted tissue such as nasal turbinate and lung.

Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice.

Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of "ChulaCov19", a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP). In female BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 µg elicits robust neutralizing antibody (NAb) and T cell responses in a dose-dependent relationship. The geometric mean titers (GMTs) of NAb against wild-type (WT, Wuhan-Hu1) virus are 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induce better cross-NAb against Delta (B.1.617.2) and Omicron (BA.1 and BA.4/5) variants. This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. In a heterologous prime-boost study, ChulaCov19 booster dose generates a 7-fold increase of NAb against Wuhan-Hu1 WT virus and also significantly increases NAb response against Omicron (BA.1 and BA.4/5) when compared to homologous CoronaVac or AZD1222 vaccination. Challenge studies show that ChulaCov19 protects human-ACE-2-expressing female mice from COVID-19 symptoms, prevents viremia and significantly reduces tissue viral load. Moreover, anamnestic NAb response is undetectable in challenge animals. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or boost vaccination and has entered clinical development.

Universal logic with encoded spin qubits in silicon.

Quantum computation features known examples of hardware acceleration for certain problems, but is challenging to realize because of its susceptibility to small errors from noise or imperfect control. The principles of fault tolerance may enable computational acceleration with imperfect hardware, but they place strict requirements on the character and correlation of errors1. For many qubit technologies2-21, some challenges to achieving fault tolerance can be traced to correlated errors arising from the need to control qubits by injecting microwave energy matching qubit resonances. Here we demonstrate an alternative approach to quantum computation that uses energy-degenerate encoded qubit states controlled by nearest-neighbour contact interactions that partially swap the spin states of electrons with those of their neighbours. Calibrated sequences of such partial swaps, implemented using only voltage pulses, allow universal quantum control while bypassing microwave-associated correlated error sources1,22-28. We use an array of six 28Si/SiGe quantum dots, built using a platform that is capable of extending in two dimensions following processes used in conventional microelectronics29. We quantify the operational fidelity of universal control of two encoded qubits using interleaved randomized benchmarking30, finding a fidelity of 96.3% ± 0.7% for encoded controlled NOT operations and 99.3% ± 0.5% for encoded SWAP. The quantum coherence offered by enriched silicon5-9,16,18,20,22,27,29,31-37, the all-electrical and low-crosstalk-control of partial swap operations1,22-28 and the configurable insensitivity of our encoding to certain error sources28,33,34,38 all combine to offer a strong pathway towards scalable fault tolerance and computational advantage.

Multicentre open label randomised controlled trial of immediate enhanced ambulatory ECG monitoring versus standard monitoring in acute unexplained syncope patients: the ASPIRED study.

INTRODUCTION: Diagnosing underlying arrhythmia in emergency department (ED) syncope patients is difficult. There is a evidence that diagnostic yield for detecting underlying arrhythmia is highest when cardiac monitoring devices are applied early, ideally at the index visit. This strategy has the potential to change current syncope management from low diagnostic yield Holter to higher yield ambulatory monitoring, reduce episodes of syncope, reduce risk of recurrence and its potential serious consequences, reduce hospital admissions, reduce overall health costs and increase quality of life by allowing earlier diagnosis, treatment and exclusion of clinically important arrhythmias. METHODS AND ANALYSES: This is a UK open prospective parallel group multicentre randomised controlled trial of an immediate 14-day ambulatory patch heart monitor vs standard care in 2234 patients presenting acutely with unexplained syncope. Our patient focused primary endpoint will be number of episodes of syncope at 1 year. Health economic evaluation will estimate the incremental cost per syncope episode avoided and quality-adjusted life year gained. ETHICS AND DISSEMINATION: Informed consent for participation will be sought. The ASPIRED trial received a favourable ethical opinion from South East Scotland Research Ethics Committee 01 (21/SS/0073). Results will be disseminated via scientific publication, lay summary and visual abstract. TRIAL REGISTRATION NUMBER: ISRCTN 10278811.

A Digital Health Intervention for Concussion: Development and Clinical Feasibility Study.

BACKGROUND: Concussion is a common condition that can lead to a constellation of symptoms that affect quality of life, social integration, and return to work. There are several evidence-based behavioral and psychological interventions that have been found to improve postconcussion symptom burden. However, these are not routinely delivered, and individuals receive limited support during their concussion recovery. OBJECTIVE: This study aimed to develop and test the feasibility of a digital health intervention using a systematic evidence-, theory-, and person-based approach. METHODS: This was a mixed methodology study involving a scoping review (n=21), behavioral analysis, and logic model to inform the intervention design and content. During development, the intervention was optimized with feedback from individuals who had experienced concussions (n=12) and health care professionals (n=11). The intervention was then offered to patients presenting to the emergency department with a concussion (n=50). Participants used the intervention freely and input symptom data as part of the program. A number of outcome measures were obtained, including participant engagement with the intervention, postconcussion symptom burden, and attitudes toward the intervention. A selection of participants (n=15) took part in in-depth qualitative interviews to understand their attitudes toward the intervention and how to improve it. RESULTS: Engagement with the intervention functionality was 90% (45/50) for the symptom diary, 62% (31/50) for sleep time setting, 56% (28/50) for the alcohol tracker, 48% (24/50) for exercise day setting, 34% (17/50) for the thought diary, and 32% (16/50) for the goal setter. Metrics indicated high levels of early engagement that trailed off throughout the course of the intervention, with an average daily completion rate of the symptom diary of 28.23% (494/1750). A quarter of the study participants (13/50, 26%) were classified as high engagers who interacted with all the functionalities within the intervention. Quantitative and qualitative feedback indicated a high level of usability and positive perception of the intervention. Daily symptom diaries (n=494) demonstrated a wide variation in individual participant symptom burden but a decline in average burden over time. For participants with Rivermead scores on completion of HeadOn, there was a strong positive correlation (r=0.86; P<.001) between their average daily HeadOn symptom diary score and their end-of-program Rivermead score. Insights from the interviews were then fed back into development to optimize the intervention and facilitate engagement. CONCLUSIONS: Using this systematic approach, we developed a digital health intervention for individuals who have experienced a concussion that is designed to facilitate positive behavior change. Symptom data input as part of the intervention provided insights into postconcussion symptom burden and recovery trajectories. TRIAL REGISTRATION: ClinicalTrials.gov NCT05069948; https://clinicaltrials.gov/ct2/show/NCT05069948.

Identification of mosquito proteins that differentially interact with alphavirus nonstructural protein 3, a determinant of vector specificity.

Chikungunya virus (CHIKV) and the closely related onyong-nyong virus (ONNV) are arthritogenic arboviruses that have caused significant, often debilitating, disease in millions of people. However, despite their kinship, they are vectored by different mosquito subfamilies that diverged 180 million years ago (anopheline versus culicine subfamilies). Previous work indicated that the nonstructural protein 3 (nsP3) of these alphaviruses was partially responsible for this vector specificity. To better understand the cellular components controlling alphavirus vector specificity, a cell culture model system of the anopheline restriction of CHIKV was developed along with a protein expression strategy. Mosquito proteins that differentially interacted with CHIKV nsP3 or ONNV nsP3 were identified. Six proteins were identified that specifically bound ONNV nsP3, ten that bound CHIKV nsP3 and eight that interacted with both. In addition to identifying novel factors that may play a role in virus/vector processing, these lists included host proteins that have been previously implicated as contributing to alphavirus replication.