Flow Device Research Articles

Active compound particles in a quadratic flow: hydrodynamics and morphology.

Generating core-shell particles with a well-controlled morphology is of great interest due to the interdependence between the morphology and different properties of these structures. These particles are often generated in microfluidic devices in a background quadratic flow. Therefore, in this study, we investigate the hydrodynamics and morphology of a concentric active compound particle, an active particle encapsulated in a fluid droplet, in an imposed quadratic flow. Governing equations for fluid flow are analytically solved in the inertia-less limit assuming that the surface tension force dominates the viscous forces (capillary number, Ca ≪ 1). Poiseuille flow deforms the compound particle into a three-lobe structure governed by the hexapolar component of the Poiseuille flow. Activity deforms the compound particle into a prolate shape owing to the velocity field of a force dipole. For an active compound particle in a Poiseuille flow, morphology is sensitive to the orientations and relative strengths of the activity and Poiseuille flow. Primarily, the presence of activity breaks the three-lobe symmetry of the drop shape and makes it more asymmetric and elongated. Moreover, the active compound particle becomes more susceptible to breakup in a quadratic flow when (i) the strength of activity is much stronger than the imposed flow strength, (ii) the active particle is oriented along the symmetry axes of the quadratic flow, (iii) the size ratio of the confining droplet to the encapsulated active particle is small and (iv) the viscosity ratio of the outer fluid to the inner fluid is small. Finally, we demonstrate that imposing the pulsatile quadratic flow prevents the breakup of an active compound particle during its generation and transport, and further assists in tuning the morphology.

The 2D microfluidics cookbook - modeling convection and diffusion in plane flow devices.

A growing number of microfluidic systems operate not through networks of microchannels but instead through using 2D flow fields. While the design rules for channel networks are already well-known and exposed in microfluidics textbooks, the knowledge underlying transport in 2D microfluidics remains scattered piecemeal and is not easily accessible to experimentalists and engineers. In this tutorial review, we formulate a unified framework for understanding, analyzing and designing 2D microfluidic technologies. We first show how a large number of seemingly different devices can all be modelled using the same concepts, namely flow and diffusion in a Hele-Shaw cell. We then expose a handful of mathematical tools, accessible to any engineer with undergraduate level mathematics knowledge, namely potential flow, superposition of charges, conformal transforms and basic convection-diffusion. We show how these tools can be combined to obtain a simple "recipe" that models almost any imaginable 2D microfluidic system. We end by pointing to more advanced topics beyond 2D microfluidics, namely interface problems and flow and diffusion in the third dimension. This forms the basis of a complete theory allowing for the design and operation of new microfluidic systems.

Study on the hydrodynamic characteristics of swirl flow device

The work examined the hydrodynamic situation, which is created by the interaction of reciprocal twisted flows and the distribution of axial velocity along the radius of the primary and secondary flow inputs and the radius of the exhaust pipe in order to create a complete physical picture. Determination of the radius distribution of the static pressure values determined by the height of the apparatus and the static pressure distribution in the exhaust pipe.

A rapid method for DNA Isolation from blood, dried blood spots and rapid diagnosis test.

Malaria is a parasitic disease spread by Plasmodium parasite. Microscopy, lateral flow devices such as the Rapid Diagnostic Test (RDT), molecular methods such as Polymerase Chain Reaction (PCR), isothermal methods such as Loop-mediated isothermal amplification (LAMP), and other diagnostic methods are available for malaria. On the other hand, the accuracy of molecular diagnosis is dependent on genomic DNA isolation. A quick method for isolating and subjectively determining the presence of genomic DNA from blood, dried blood spot (DBS), and rapid diagnostic test (RDT), was identified. We have developed a protocol for isolating DNA from blood, DBS, and RDTs using the HUDSON Buffer (TCEP and EDTA). Isolated genomic DNA was seen with SYBR Safe DNA stain (1X) under a UV transilluminator without running in 0.8 percent gel electrophoresis or using a spectrophotometer. The technique for DNA isolation was accurate for the presence of malaria parasite genomic DNA from positive samples confirmed by microscopy with a sensitivity of 76% and specificity of 78.67% and RDT with a sensitivity of 88% and specificity of 66%. The requirements were minimal, and the process took 30 minutes for a hundred sample processing. Finding a fast and reliable method of separating nucleic acids from many samples is crucial. This approach extracts intact genomic DNA in under ten minutes, making it ideal for large-scale investigations.

Flow control in paper-based microfluidic channel by using hydrophobic tape barrier on the paper surface

Paper-based microfluidics offers a simple, cost-effective, and versatile platform for fluid manipulation and analysis. Despite significant advancements in paper fluidics, the flow control in paper channel remains a challenging task. In this regard, we have developed a flow delay channel in paper using rectangular tape patterns on the paper surface. We have investigated the effect of hydrophobic tape barriers with varying widths. The designing and cutting of the hydrophobic tape and paper channel was performed by CO2 laser machine using CorelDraw software. Once cut, the tape barriers were attached to the paper surface and then passed through the roller press machine for proper adhesion of tape pattern onto the paper’s surface. From experiments, we observed that by increasing the width of tape, the delay also increased. The hydrophobic tape on the paper surface caused resistance to the flowing fluid. Due to this surface resistance, flow velocity reduced, and the time delay increased. We believe that our novel approach will provide an alternative method of flow control for paper-based microfluidic devices and can be utilized in various food quality sensors and lateral flow devices.

Capillary driven microfluidic sequential flow device for point-of-need ELISA: COVID-19 serology testing.

A capillary-driven microfluidic sequential flow device, designed for eventual at-home or doctor's office use, was developed to perform an enzyme-linked immunosorbent assay (ELISA) for serology assays. Serology assays that detect SARS-CoV-2 antibodies can be used to determine prior infection, immunity status, and/or individual vaccination status and are typically run using well-plate ELISAs in centralized laboratories, but in this format SARs-CoV-2 serology tests are too expensive and/or slow for most situations. Instead, a point-of-need device that can be used at home or in doctor's offices for COVID-19 serology testing would provide critical information for managing infections and determining immune status. Lateral flow assays are common and easy to use, but lack the sensitivity needed to reliably detect SARS-CoV-2 antibodies in clinical samples. This work describes a microfluidic sequential flow device that is as simple to use as a lateral flow assay, but as sensitive as a well-plate ELISA through sequential delivery of reagents to the detection area using only capillary flow. The device utilizes a network of microfluidic channels made of transparency film and double-sided adhesive combined with paper pumps to drive flow. The geometry of the channels and storage pads enables automated sequential washing and reagent addition steps with two simple end-user steps. An enzyme label and colorimetric substrate produce an amplified, visible signal for increased sensitivity, while the integrated washing steps decrease false positives and increase reproducibility. Naked-eye detection can be used for qualitative results or a smartphone camera for quantitative analysis. The device detected antibodies at 2.8 ng mL-1 from whole blood, while a well-plate ELISA using the same capture and detection antibodies could detect 1.2 ng mL-1. The performance of the capillary-driven immunoassay (CaDI) system developed here was confirmed by demonstrating SARS-CoV-2 antibody detection, and we believe that the device represents a fundamental step forward in equipment-free point-of-care technology.

A multi-line platinum nanozyme-based lateral flow device for the colorimetric evaluation of total antioxidant capacity in different matrices.

The evaluation of Total Antioxidant Capacity (TAC), namely the complete pattern of antioxidant species in a complex medium, is of major interest in many fields ranging from health monitoring to quality control in the food industry. In this framework, point-of-care (POC) testing technologies are a promising diagnostic solution for rapid on-site analyses, unlike laboratory based-assays, which are often limited by centralized analyses, time-consuming and costly procedures, and invasiveness in the case of health diagnostics. In this work, we developed a POC methodology that evaluates TAC in different matrices, exploiting the peroxidase-like properties of 5 nm platinum nanoparticles (PtNPs), combined with a colorimetric paper-based device. Notably, we designed and optimized a multi-line PtNPs-based Lateral Flow Assay (LFA), which relies on three sequential test lines with increasing concentrations of platinum nanozymes, to get a non-invasive, accurate, and fast (10 minutes) colorimetric evaluation of the body TAC in saliva samples. Furthermore, we employed the device as a prototype of a quality control tool in the food industry, for the determination of the TAC in fruit juices.

Enhanced podocyte differentiation and changing drug toxicity sensitivity through pressure-controlled mechanical filtration stress on a glomerulus-on-a-chip.

Podocytes, localized in the glomerulus, are a prognostic factor of proteinuria in kidney disease and are exposed to distinct physiological stimuli from basal to apical filtration flow. Research studies on drug discovery and disease modeling for glomerulopathy have developed a glomerulus-on-a-chip and studied podocyte mechanobiology to realize alternative methods to animal experiments. However, the effect of filtration stimulus on podocytes has remained unclear. Herein, we report the successful development of a user-friendly filtration culture device and system that can precisely control the filtration flow using air pressure control by incorporating a commercially available culture insert. It allows mouse podocytes to be cultured under filtration conditions for three days with a guarantee of maintaining the integrity of the podocyte layer. Using our system, this study demonstrated that podocyte damage caused by hyperfiltration resulting from glomerular hypertension, a common pathophysiology of many glomerulopathies, was successfully recapitulated and that filtration stimulus promotes the maturation of podocytes in terms of their morphology and gene expression. Furthermore, we demonstrated that filtration stimulus induced different drug responsiveness in podocytes than those seen under static conditions, and that the difference in drug responsiveness was dependent on the pharmacological mechanism. Overall, this study has revealed differentiating and pharmacodynamic properties of filtration stimulus and brings new insights into the research field of podocyte mechanobiology towards the realization of glomerulus-on-a-chip.

Construction of a canine model with acute type B aortic dissection using a self-made pressure-driven flow device.

A reproducible canine aortic dissection (AD) model would be useful for evaluating the performance of novel endovascular treatment devices. Therefore, we attempted to create a reproducible canine model of Stanford type B AD (TBAB) by a surgical method. Computed tomography angiography was performed 2 h after the procedure to determine if a false lumen was present, and follow-up imaging was performed 10 d after the procedure using digital subtraction angiography, intravascular ultrasound (IVUS), and color Doppler flow imaging (CDFI) to confirm stable persistence of the false lumen. The success rate of model construction was 88.8% (16/18). All surviving dogs had distal re-entries (16/16). The number of re-entries in the dogs was 1.50 ± 0.52, and the mean length of the false lumen was 175.37 ± 16.98 mm. IVUS showed the area of the false lumen at the narrowest part of the arterial lumen was 84.88 ± 1.27%. The CDFI showed that the peak systolic velocity in the false lumen (10.89 ± 0.74 cm/s) was significantly slower than that in the true lumen (25.31 ± 1.72 cm/s; P<0.001). Moreover, the direction of blood flow in the true lumen was consistent, whereas that in the false lumen was disordered. We optimized the traditional surgical method to construct a canine model of TBAD to improve the success rate of model construction, and designed a novel device to lengthen the false lumen. The proposed model has wide implications in evaluating the performance of novel endovascular treatment devices and studying the AD-related hemodynamics.

Understanding the leading indicators of hospital admissions from COVID-19 across successive waves in the UK.

Following the end of universal testing in the UK, hospital admissions are a key measure of COVID-19 pandemic pressure. Understanding leading indicators of admissions at the National Health Service (NHS) Trust, regional and national geographies help health services plan for ongoing pressures. We explored the spatio-temporal relationships of leading indicators of hospitalisations across SARS-CoV-2 waves in England. This analysis includes an evaluation of internet search volumes from Google Trends, NHS triage calls and online queries, the NHS COVID-19 app, lateral flow devices (LFDs), and the ZOE app. Data sources were analysed for their feasibility as leading indicators using Granger causality, cross-correlation, and dynamic time warping at fine spatial scales. Google Trends and NHS triages consistently temporally led admissions in most locations, with lead times ranging from 5 to 20 days, whereas an inconsistent relationship was found for the ZOE app, NHS COVID-19 app, and LFD testing, which diminished with spatial resolution, showing cross-correlation of leads between -7 and 7 days. The results indicate that novel surveillance sources can be used effectively to understand the expected healthcare burden within hospital administrative areas though the temporal and spatial heterogeneity of these relationships is a key determinant of their operational public health utility.

Simulation of lutetium metal evaporation with considering atomic metastable state

Lutetium-177, one of the current global research hotspots for medical isotopes, can be produced by reactor irradiation of lutetium-176, which can be produced and processed with the assistance of the electron beam physical vapor deposition (EB-PVD). The metal evaporation process is an important part of EB-PVD, which aims to convert solid metal into metal atomic vapor. The distribution of each macroscopic characteristic quantity, such as thermal population distribution, density distribution, velocity distribution, and temperature distribution of metal atomic vapor, will directly affect the utilization of metal vapor atoms, the subsequent deposition process, and coating process. In this paper, two-dimensional model and three-dimensional model of the metal evaporation process are established based on the direct simulation Monte Carlo method, and atomic metastable state is introduced into the collision assumption. The macroscopic characteristic quantities, such as the number density of metal atomic vapor, the motion velocity and the discrete degree of the total motion velocity in the evaporation process with or without considering the lutetium atomic metastable state, are analyzed and compared. The spatial distribution characteristics of each energy level of metal atomic vapor are observed, and the variation characteristics of the macroscopic characteristic quantities in the center with the slit opening size and the evaporation source surface temperature are discussed. The study results show that the number density of metal vapor passing through the beam flow device decreases, the average velocity in the &lt;i&gt;x&lt;/i&gt;-direction and &lt;i&gt;z&lt;/i&gt;-direction and the discrete degree of the total motion velocity increase, with the atomic metastable state taken into consideration. The beam flow device intensifies the transformation of the atomic energy level of the metal vapor and changes the physical parameters of the metal atomic vapor. At the same time, the slit opening size and the evaporation source surface temperature trigger off the change of the macroscopic characteristic quantity distribution of the metal vapor, including the degree of anomalous protrusion of each macroscopic characteristic quantity above the slit. The results of the three-dimensional simulation based on the two-dimensional model are consistent with the changes in the order of magnitude of data distribution and spatial distribution pattern, which can serve as a reference and guidance for the experimental study of the electron beam metal evaporation process.

Development of a lateral flow device for rapid simultaneous multiple detections of some common bacterial causes of bovine mastitis.

This work was conducted for the development of a 5-combi lateral flow immunochromatographic kit (LFK) for rapid and simultaneous identification of the common bacterial causes of bovine mastitis. The following pathogens are the identification targets of this kit: Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus agalactiae, and Streptococcus pyogenes in milk samples from suspected bovine mastitis cases. The conventional microbiological identification of these agents is not only time-consuming and requires a fully equipped laboratory but also requires experienced personnel. Rabbit polyclonal antibodies (PAbs) specific to the antigenic components of the selected pathogens were prepared, and the pathogen-specific IgG was separated, purified, and conjugated with nanogold that was laid on the conjugate pad. Guinea pig PAbs specific to the microbial antigens of the selected pathogens were prepared, and their IgG content was separated, purified, and used as a capture antibody in the test (T) line on the nitrocellulose (NC) strips. Goat anti-rabbit IgG antibodies were used to capture the rabbit antibodies in the control (C) line of NC strips. The kit was held in a device comprising five strip-holding channels for the above-mentioned five bacterial species antigens. The developed LFK was evaluated, and its sensitivity and specificity were determined. The developed kits were applied for the examination of bovine milk samples from suspected mastitis cases, and the average sensitivity, specificity, and accuracy of 5-combi LFK for the detection of the five selected bacterial species compared to bacteriological examination (gold standard test) were 93.90%, 80.83%, and 90.53%, respectively. The minimal microbial count that gave positive results using the developed LFK was 103 colony forming unit/ml. Treatment of the milk samples with an application buffer and its pre-incubation in trypticase soy broth for 6 h at 37°C before testing significantly increased the sensitivity of the prepared LFK. The developed kit proved simple and convenient, and the results could be obtained in less than 10 min.

Lateral flow assay of pathogenic viruses and bacteria in healthcare.

Healthcare-associated pathogenic viruses and bacteria can have a serious impact on human health and have attracted widespread global attention. The lateral flow assay is a unidirectional detection based on the binding of a target analyte and a bioreceptor on the device via lateral flow. With incredible advantages over traditional chromatographic methods, such as rapid detection, ease of manufacture and cost effectiveness, these test strips are increasingly considered the ideal form for point-of-care applications. This review explores lateral flow assays for pathogenic viruses and bacteria, with a particular focus on methodologies, device components, construction methods, and applications. We anticipate that this review could provide exciting opportunities for developing new lateral flow devices for pathogens and advance related healthcare applications.

Sustainable removal of uranium from acidic wastewater using various mineral raw materials

Various types of plutonic and volcanic rocks and their alteration products from Greece (serpentinite, magnesite and andesite), have been used for sustainable removal of Uranium (U) from the acidic drainage of Kirki mine, as well as for the pH increase of the polluted solutions. In this light, this study aims at the further understanding and improvement of the ecofriendly reuse of sterile, natural raw materials (including those remaining through industrial processing and engineering testing of aggregate rocks), for remediation of acid mine drainage. The selected rocks constitute such residues of sterile materials were used as filters in experimental continuous flow devices in the form of batch-type columns, in order to investigate acidic remediation properties with special focus on U removal. The initial pH of the wastewater was 2.90 and increased after seven (7) days of experimental application and more specifically from the fourth day onwards. Uranium removal became quantitatively significant once pH reached the value of 5.09. The volcanic rocks appeared to be more effective for U removal than the plutonic ones because of microtextural differences. However, optimum U removal was mainly achieved by serpentinite: while the raw materials rich in Mg strongly reacted and remediated the pH of the drainage water waste. Furthermore, the increase of pH values due to the presence of mineral raw materials, provided increased oxidation potential which deactivated the toxic load of metals, particularly U. Consequently, batch-type serpentinite reaction with the tailing fluid caused a drop in U concentration from an initial value of 254 ppb to the one of 8 ppb, which corresponds to 97% of removal. Andesite presented the second best reactant for experimental remediation, especially when it was mixed with magnetically separated mineral fractions. Despite the fact that the proposed methodology is currently at a relatively low Technology Readiness Level (TRL), it carries the potential to become an extremely effective and low-cost alternative to conventional environmental restoration technologies.

Numerical simulation of performance of traveling wave pump-turbine at different wave speeds in pumping mode

Fish swim by flexing their bodies and energy is transferred from the fish to the water. And the plate which imitates traveling wave motion of fish can absorb the energy of fluid under certain motion parameters. By arranging the traveling wave plate in a vertical rectangular flow channel, the flow mode is changed from external flow mode to internal flow mode. This internal flow device is called traveling wave pump-turbine, and it can operate in both pumping mode and turbine mode. The traveling wave plate is simplified into a two-dimensional plate, and the model of the traveling wave pump-turbine is established. The numerical simulation method is used to study its performance characteristics at different wave speeds when it is in pumping mode. The results show that: although it operates in pumping mode by changing the volume of the working chamber, it can output stable mass flow rate. With the increase of wave speed, the volumetric efficiency increases gradually, the time-averaged efficiency first increases and then decreases, and the maximum time-averaged efficiency can reach 0.9. The instantaneous pressure and power are relatively stable when the wave speed is low, while they fluctuate more sharply with the increase of wave speed.

Kinetic Profiling of Homogeneous and Heterogeneous Biocatalysts in Continuous Flow by Online Mass Spectrometry.

Enzyme kinetics is normally assessed by performing individual kinetic measurements using batch-type reactors (test tubes, microtiter plates), in which enzymes are mixed with different substrates. Some drawbacks of conventional methods are the large amounts of experimental materials, long analysis times, and limitations of spectrophotometry. Therefore, we have developed a method for facile determination of enzyme kinetics using online flow-based mass spectrometry. A concentration ramp of substrate or product was created by dynamically adjusting flow rates of pumps delivering stock solution of substrate and diluent. Precise kinetic measurements were performed by reaction product quantification and initial rate calculation. In the presence of ascending substrate concentrations, the rate of a target enzyme (penicillinase)-catalyzed hydrolysis was varied. By measuring the reaction product continuously, Michaelis constants (KM) could be calculated. The enzyme kinetic measurements for hydrolysis of penicillins were conducted based on this simple, rapid, and low sample consumption online flow device. In the homogeneous reaction, the KM values for amoxicillin, ampicillin, penicillin G, and penicillin V were 254.9 ± 14.5, 29.2 ± 0.3, 2.6 ± 0.1, and 5.4 ± 0.1 μM, respectively. In the heterogeneous reaction, the KM values for amoxicillin, ampicillin, penicillin G, and penicillin V were 408.9 ± 75.1, 114.4 ± 8.0, 21.8 ± 0.7, and 83.3 ± 4.8 μM, respectively. Apart from enzyme assay, the showcased method for the generation of temporal concentration ramps can be utilized to perform rapid quantity calibrations for mass spectrometric analyses.

An Automated Computer-Vision "Bubble-Counting" Technique to Characterise CO2 Dissolution into an Acetonitrile Flow Stream in a Teflon AF-2400 Tube-in-Tube Flow Device.

Invited for this month's cover is the group of Matt O'Brien at Keele University. The cover picture shows a depiction of 'computer vision' in the context of CO2 dissolution into tube-in-tube membrane devices in continuous flow. The original manuscript is part of the Special Collection on "Automation in Chemistry and Beyond" and more information can be found in the Research Article by Matthew O'Brien and Ruxandra Moraru.

Detection of SARS-CoV-2 Virus by Triplex Enhanced Nucleic Acid Detection Assay (TENADA)

SARS-CoV-2, a positive-strand RNA virus has caused devastating effects. The standard method for COVID diagnosis is based on polymerase chain reaction (PCR). The method needs expensive reagents and equipment and well-trained personnel and takes a few hours to be completed. The search for faster solutions has led to the development of immunological assays based on antibodies that recognize the viral proteins that are faster and do not require any special equipment. Here, we explore an innovative analytical approach based on the sandwich oligonucleotide hybridization which can be adapted to several biosensing devices including thermal lateral flow and electrochemical devices, as well as fluorescent microarrays. Polypurine reverse-Hoogsteen hairpins (PPRHs) oligonucleotides that form high-affinity triplexes with the polypyrimidine target sequences are used for the efficient capture of the viral genome. Then, a second labeled oligonucleotide is used to detect the formation of a trimolecular complex in a similar way to antigen tests. The reached limit of detection is around 0.01 nM (a few femtomoles) without the use of any amplification steps. The triplex enhanced nucleic acid detection assay (TENADA) can be readily adapted for the detection of any pathogen requiring only the knowledge of the pathogen genome sequence.

A Universal Device to Convert a Continuous Flow Assist Device to a Pulsatile Flow Device to Simulate Normal Blood Flow and Pressure Patterns.

Continuous follow assist devices (CFAD) are the most commonly used mechanical circulatory support devices. Compared to Pulsatile flow assist devices (PFAD), CFADs deliver a non-physiologic type of flow, which might contribute to complications related to lack of pulsatility in these devices. Moreover, lack of pulsatility complicates the clinical management of these patients who often present with good perfusion but with no palpable pulse and none or a negligible pulse pressure on blood pressure measurement. Presented here is a concept of a universal converter device that can be added inline other CFADs to convert the flow from continuous to pulsatile, simulating a normal flow and pressure pattern. After initial implantation and stabilization with a CFAD, adding this converter might potentially provide the benefits of pulsatile physiologic flow. The device is made of 2 components connected in parallel, working in tandem in user determined cycles. The continuous flow through a specifically positioned openings create a smooth conversion to a pulsatile flow. This device can convert a continuous flow to a physiologic pulsatile flow to achieve a native-like flow pattern and potentially prevent some CFAD complications. This paper presents the concept of pulsatility generation and simulation for other assist devices. Such a device can be a universal add-on or a supplemental option for CFADs.

The Performance of Lateral Flow Tests in the Age of the Omicron: A Rapid Systematic Review.

Prompt detection and isolation of COVID-19 cases is vital for preventing further viral transmission, and lateral flow or rapid antigen tests have been an important diagnostic tool in this pandemic. However, concerns have emerged regarding the sensitivity of these devices for the new BA.1, BA.2, and BA.4/5 omicron variants, which have greater transmissibility and extensive mutations in its spike (S) and nucleocapsid (N) proteins. N protein is an important target protein for existing lateral flow devices. This paper therefore aimed to provide a rapid review of available literature on the performance of the lateral flow tests for detecting the omicron coronavirus variant. A systematic literature search of PubMed, EMBASE, OVID Medline, and Google Scholar found six published studies and four preprints investigating the performance of existing lateral flow devices for the omicron variant, as compared to the B.1.617.2 (Delta) variant. Overall, it appears that the devices have poorer performance for the omicron variant and when testing samples with cycle threshold (Ct) values greater than 25 and in asymptomatic individuals. As most available data were preliminary and had small sample sizes, it is recommended that these data be further studied to better inform and adapt our public health responses.