Composition of Anopheles species and bionomic characteristics over the peak malaria transmission season in Bandarban, Bangladesh.

BACKGROUND: Joint efforts by government and non-government organizations have helped to reduce malaria in Bangladesh and set the country on a clear path to eventual malaria elimination. However, achieving that goal would be challenging without a comprehensive understanding of vector bionomics. METHODS: Targeted capturing of Anopheles mosquitoes over a rainy season, utilizing specific sampling methods, including human landing catches (HLCs), CDC-light traps (CDC-LTs), and pyrethrum spray catches (PSCs) were aimed to characterize entomological drivers of transmission in four sites of Bandarban, Bangladesh. RESULTS: Molecular characterization of a subset of 4637 mosquitoes has demonstrated the presence of at least 17 species whose capture rates were representative of the rainy season. Species compositions and bionomic traits did not vary between sites with Anopheles maculatus having the highest landing rate by HLCs and Anopheles vagus having the highest capture rate with CDC-LTs. Interestingly, Anopheles species compositions and capture rates varied significantly (p < 0.05) for An. vagus, between HLCs and its often-used proxy-CDC-LTs- suggesting impacts on downstream analysis. CDC-LTs capture rates demonstrated differing compositions with indoor and outdoor biting rates. For example, Anopheles nigerrimus and Anopheles nivipes were more endophagic by HLCs and more exophagic by CDC-LTs. The use of a cow-baited CDC-LT also demonstrated significantly different results when compared to a human-baited CDC-LT considering the high degree of anthropophily in these species. The exception to both zoophily and indoor resting was An. vagus, which demonstrated both anthropophily and high resting rates indoors-pointing to this species being a possible primary vector at this site. CONCLUSION: A diverse Anopheles fauna in Bandarban has been confirmed through molecular methods, highlighting the potential impact of sampling techniques. Given the complexity of the local ecosystem, a better understanding of mosquito behaviour and ecology is required to achieve the goal of malaria elimination in Bangladesh.

Observation of Tissue Oxygenation Changes Using Remote Photoplesysmography with a Smartphone.

BACKGROUND: Tissue oxygenation is a critical marker of tissue status and can be used to evaluate and track wound progress, the viability of transplanted tissue, and burns. Thus, the determination of tissue oxygenation (preferably remotely) is of great importance. AIM: Explore the impact of oxygenation changes on tissue color. MATERIAL AND METHODS: The rPPG of both hands was acquired using a stand-mounted smartphone (iPhone 8) placed about 10 cm above the hands. A 60 s baseline was followed by occlusion of one arm using a cuff inflated to 200 mmHg for approximately 2 min. The cuff was then rapidly deflated, followed by a 60 s recovery period. The reference muscle oxygenation signal (SmO2) was acquired using the near-infrared contact Moxy device (Fortiori Design LLC) placed on the forearm distal to the occlusion. The data were collected on both hands of 28 healthy volunteers. RESULTS: rPPG can observe changes in tissue oxygenation, which was confirmed across 28 participants using a robust reference standard. CONCLUSION: We have an initial confirmation of the notion that rPPG can monitor changes in tissue oxygenation. However, a spectrum of rPPG and SmO2 reductions is observed, which should be explored in future work.

Remote Photoplethysmography with a High-Speed Camera Reveals Temporal and Amplitude Differences between Glabrous and Non-Glabrous Skin.

Photoplethysmography (PPG) is a noninvasive optical technology with applications including vital sign extraction and patient monitoring. However, its current use is primarily limited to heart rate and oxygenation monitoring. This study aims to demonstrate the utility of PPG for physiological investigations. In particular, we sought to demonstrate the utility of simultaneous data acquisition from several regions of tissue using remote/contactless PPG (rPPG). Specifically, using a high-speed scientific-grade camera, we collected rPPG from the hands (palmar/dorsal) of 22 healthy volunteers. Data collected through the red and green channels of the RGB CMOS sensor were analyzed. We found a statistically significant difference in the amplitude of the glabrous skin signal over the non-glabrous skin signal (1.41 ± 0.85 in the red channel and 2.27 ± 0.88 in the green channel). In addition, we found a statistically significant lead of the red channel over the green channel, which is consistent between glabrous (17.13 ± 10.69 ms) and non-glabrous (19.31 ± 12.66 ms) skin. We also found a statistically significant lead time (32.69 ± 55.26 ms in the red channel and 40.56 ± 26.97 ms in the green channel) of the glabrous PPG signal over the non-glabrous, which cannot be explained by bilateral variability. These results demonstrate the utility of rPPG imaging as a tool for fundamental physiological studies and can be used to inform the development of PPG-based devices.

Impact of a spatial repellent product on Anopheles and non-Anopheles mosquitoes in Sumba, Indonesia.

BACKGROUND: The East Nusa Tenggara province, Indonesia, contributed to 5% of malaria cases nationally in 2020, with other mosquito-borne diseases, such as dengue and filariasis also being endemic. Monitoring of spatial and temporal vector species compositions and bionomic traits is an efficient method for generating evidence towards intervention strategy optimization and meeting disease elimination goals. METHODS: The impact of a spatial repellent (SR) on human biting mosquitoes was evaluated as part of a parent cluster-randomized, double-blinded, placebo-controlled trial, in Sumba, East Nusa Tenggara. A 10-month (June 2015-March 2016) baseline study was followed by a 24-month intervention period (April 2016 to April 2018)-where half the clusters were randomly assigned either a passive transfluthrin emanator or a placebo control. RESULTS: Human-landing mosquito catches documented a reduction in landing rates related to the SR. Overall, there was a 16.4% reduction (21% indoors, and 11.3% outdoors) in human biting rates (HBR) for Anopheles. For Aedes, there was a 44.3% HBR reduction indoors and a 35.6% reduction outdoors. This reduction was 38.3% indoors and 39.1% outdoors for Armigeres, and 36.0% indoors and 32.3% outdoors for Culex species. Intervention impacts on the HBRs were not significant and are attributed to large inter-household and inter cluster variation. Anopheles flavirostris, Anopheles balabacensis and Anopheles maculatus individually impacted the overall malaria infections hazard rate with statistically significance. Though there was SR-based protection against malaria for all Anopheles species (except Anopheles sundaicus), only five (Anopheles aconitus, Anopheles kochi, Anopheles tessellatus, An. maculatus and An. sundaicus) demonstrated statistical significance. The SR numerically reduced Anopheles parity rates indoors and outdoors when compared to the placebo. CONCLUSION: Evidence demonstrating that Anopheles vectors bite both indoors and outdoors indicates that currently implemented indoor-based vector control tools may not be sufficient to eliminate malaria. The documented impact of the SR intervention on Aedes, Armigeres and Culex species points to its importance in combatting other vector borne diseases. Studies to determine the impact of spatial repellents on other mosquito-borne diseases is recommended.

Feasibility Study of Remote Contactless Perfusion Imaging with Consumer-Grade Mobile Camera.

A non-invasive, contactless, inexpensive and easy-to-operate perfusion imaging method using a consumer-grade mobile camera (iPhone 8) developed in our group can visualise blood flow in tissue. METHODS: Ischemia was induced in one hand using a blood pressure cuff inflated over the systolic blood pressure to stop the blood flow. Using an iPhone, data was collected from 5 subjects, beginning with no occlusion (a baseline), followed by one hand occluded, and then release of the occlusion to restore blood circulation. This protocol was repeated for each hand for a total of 10 videos. The data were analysed to extract the oscillating and quasi-constant components of the photoplethysmogram signal representing blood flow. In addition, we introduced a scoring parameter to reflect perfusion (i.e., perfusion score). RESULTS: The proposed perfusion score was used to create a pseudo colour map of perfusion across the protocol, demonstrating the ability to detect ischemia caused by occlusion. The difference in perfusion score was statistically significant between ischemia and baseline/recovery. CONCLUSIONS: Pilot results on healthy volunteers demonstrate the feasibility of perfusion imaging using a consumer-grade camera. A further developed method can be used to assess the viability of transplanted tissue.

Towards Development of Specular Reflection Vascular Imaging.

Specular reflection from tissue is typically considered as undesirable, and managed through device design. However, we believe that specular reflection is an untapped light-tissue interaction, which can be used for imaging subcutaneous blood flow. To illustrate the concept of subcutaneous blood flow visualization using specular reflection from the skin, we have developed a ray tracing for the neck and identified conditions under which useful data can be collected. Based on our model, we have developed a prototype Specular Reflection Vascular Imaging (SRVI) device and demonstrated its feasibility by imaging major neck vessels in a case study. The system consists of a video camera that captures a video from a target area illuminated by a rectangular LED source. We extracted the SRVI signal from 5 × 5 pixels areas (local SRVI signal). The correlations of local SRVIs to the SRVI extracted from all pixels in the target area do not appear to be randomly distributed, but rather form cohesive sub-regions with distinct boundaries. The obtained waveforms were compared with the ECG signal. Based on the time delays with respect to the ECG signal, as well as the waveforms themselves, the sub-regions can be attributed to the jugular vein and carotid artery. The proposed method, SRVI, has the potential to contribute to extraction of the diagnostic information that the jugular venous pulse can provide.

Anopheles drivers of persisting malaria transmission in Guna Yala, Panamá: an operational investigation.

BACKGROUND: Though most of Panamá is free from malaria, localized foci of transmission persist, including in the Guna Yala region. Government-led entomological surveillance using an entomological surveillance planning tool (ESPT) sought to answer programmatically-relevant questions that would enhance the understanding of both local entomological drivers of transmission and gaps in protection that result in persisting malaria transmission to guide local vector control decision-making. METHODS: The ESPT was used to design a sampling plan centered around the collection of minimum essential indicators to investigate the relevance of LLINs and IRS in the communities of Permé and Puerto Obaldía, Guna Yala, as well as to pinpoint any remaining spaces and times where humans are exposed to Anopheles bites (gaps in protection). Adult Anopheles were collected at three time points via human landing catches (HLCs), CDC Light Traps (LT), and pyrethrum spray catches (PSCs) during the rainy and dry seasons. Mosquitoes were identified to species via molecular methods. Insecticide susceptibility testing of the main vector species to fenitrothion was conducted. RESULTS: In total, 7537 adult Anopheles were collected from both sites. Of the 493 specimens molecularly confirmed to species, two thirds (n = 340) were identified as Nyssorhynchus albimanus, followed by Anopheles aquasalis. Overall Anopheles human biting rates (HBRs) were higher outdoors than indoors, and were higher in Permé than in Puerto Obaldía: nightly outdoor HBR ranged from 2.71 bites per person per night (bpn) (Puerto Obaldía), to 221.00 bpn (Permé), whereas indoor nightly HBR ranged from 0.70 bpn (Puerto Obaldía) to 81.90 bpn (Permé). Generally, peak biting occurred during the early evening. The CDC LT trap yields were significantly lower than that of HLCs and this collection method was dropped after the first collection. Pyrethrum spray catches resulted in only three indoor resting Anopheles collected. Insecticide resistance (IR) of Ny. albimanus to fenitrothion was confirmed, with only 65.5% mortality at the diagnostic time. CONCLUSION: The early evening exophagic behaviour of Anopheles vectors, the absence of indoor resting behaviours, and the presence of resistance to the primary intervention insecticide demonstrate limitations of the current malaria strategy, including indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), and point to both gaps in protection and to the drivers of persisting malaria transmission in Guna Yala. These findings highlight the need for continued and directed entomological surveillance, based on programmatic questions, that generates entomological evidence to inform an adaptive malaria elimination strategy.

Comparative evaluation of anopheline sampling methods in three localities in Indonesia.

BACKGROUND: The effectiveness of vector control efforts can vary based on the interventions used and local mosquito behaviour and adaptability. In many settings, biting patterns of Anopheles mosquitoes can shift in response to interventions targeting indoor-biting mosquitoes, often resulting in higher proportions of mosquitoes feeding outside or at times when people are not protected. These behaviourally resistant mosquitoes have been shown to sustain residual malaria transmission and limit control efforts. Therefore, it is important to accurately sample mosquitoes to understand their behaviour. METHODS: A variety of traps were evaluated in three geographically diverse sites in malaria-endemic Indonesia to investigate local mosquito feeding behaviour and determine effective traps for surveillance. RESULTS: Eight traps were evaluated in three sites: Canti village, Lampung, Kaliharjo village, Purworejo, and Saketa village, Halmahera, Indonesia, including the gold standard human landing collection (HLC) and a variety of traps targeting host-seeking and resting mosquitoes both indoors and outdoors. Trapping, using indoor and outdoor HLC, the Ifakara tent trap C, goat and human-occupied tents, resting pots and boxes, and CDC miniature light traps was conducted for 16 nights in two sites and 8 nights in a third site, using a Latin square design. Trap efficacy varied by site, with outdoor HLC yielding the highest catch rates in Canti and Kaliharjo and a goat-baited tent trap proving most effective in Saketa. In Canti village, anthropophilic Anopheles sundaicus were caught indoors and outdoors using HLCs, peaking in the early morning. In Kaliharjo, a variety of mosquitoes were caught, mostly outdoors throughout the night. HLC was ineffective in Saketa, the only site where a goat-baited tent trap was tested. This trap was effective in catching zoophilic vectors outdoors before midnight. CONCLUSIONS: Different trapping methods were suitable for different species, likely reflecting differences in behaviour among species. The three villages, each located on a different island in the Indonesian archipelago, contained mosquito populations with unique behaviours. These data suggest that the effectiveness of specific vector monitoring and control measures may vary by location.

Host attraction and biting behaviour of Anopheles mosquitoes in South Halmahera, Indonesia.

BACKGROUND: Indonesia is home to a variety of malaria vectors whose specific bionomic traits remain largely uncharacterized. Species-specific behaviours, such as host feeding preferences, impact the dynamics of malaria transmission and the effectiveness of vector control interventions. METHODS: To examine species-specific host attraction and feeding behaviours, a Latin square design was used to compare Anopheles mosquitoes attracted to human, cow, and goat-baited tents. Anopheles mosquitoes were collected hourly from the inside walls of each baited tent. Species were morphologically and then molecularly identified using rDNA ITS2 sequences. The head and thorax of individual specimens were analysed for Plasmodium DNA using PCR. Bloodmeals were identified using a multiplex PCR. RESULTS: A total of 1024, 137, and 74 Anopheles were collected over 12 nights in cow, goat, and human-baited tents, respectively. The species were identified as Anopheles kochi, Anopheles farauti s.s., Anopheles hackeri, Anopheles hinesorum, Anopheles indefinitus, Anopheles punctulatus, Anopheles tessellatus, Anopheles vagus, and Anopheles vanus, many of which are known to transmit human malaria. Molecular analysis of blood meals revealed a high level of feeding on multiple host species in a single night. Anopheles kochi, An. indefinitus, and An. vanus were infected with Plasmodium vivax at rates comparable to primary malaria vectors. CONCLUSIONS: The species distributions of Anopheles mosquitoes attracted to human, goat, and cow hosts were similar. Eight of nine sporozoite positive samples were captured with animal-baited traps, indicating that even predominantly zoophilic mosquitoes may be contributing to malaria transmission. Multiple host feeding and flexibility in blood feeding behaviour have important implications for malaria transmission, malaria control, and the effectiveness of intervention and monitoring methods, particularly those that target human-feeding vectors.

Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals.

BACKGROUND: Ivermectin has been proposed as a novel malaria transmission control tool based on its insecticidal properties and unique route of acquisition through human blood. To maximize ivermectin's effect and identify potential resistance/tolerance mechanisms, it is important to understand its effect on mosquito physiology and potential to shift mosquito population age-structure. We therefore investigated ivermectin susceptibility and gene expression changes in several age groups of female Anopheles gambiae mosquitoes. METHODS: The effect of aging on ivermectin susceptibility was analyzed in three age groups (2, 6, and 14-days) of colonized female Anopheles gambiaemosquitoes using standard survivorship assays. Gene expression patterns were then analyzed by transcriptome sequencing on an Illumina HiSeq 2500 platform. RT-qPCR was used to validate transcriptional changes and also to examine expression in a different, colonized strain and in wild mosquitoes, both of which blood fed naturally on an ivermectin-treated person. RESULTS: Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and comparing phylogeny to transcriptional patterns revealed that NPCs have rapidly evolved and separate members respond to either blood meals or to ivermectin. CONCLUSION: We present evidence of increased ivermectin susceptibility in older An. gambiae mosquitoes that had previously bloodfed. Differential expression analysis suggests complex midgut interactions resulting from ivermectin ingestion that likely involve blood meal digestion physiological responses, midgut microflora, and innate immune responses. Thus, the transcription of certain gene families is consistently affected by ivermectin ingestion, and may provide important clues to ivermectin's broad effects on malaria vectors. These findings contribute to the growing understanding of ivermectin's potential as a transmission control tool.

Design and testing of a novel, protective human-baited tent trap for the collection of anthropophilic disease vectors.

Currently, there exists a deficit of safe, active trapping methods for the collection of host-seeking Anopheles and other disease-causing arthropod vectors. The gold-standard approach for mosquito collection is that of human landing catch (HLC), in which an individual exposes bare skin to possibly infected vectors. Here, we present the development of a new method for mosquito collection, the Infoscitex tent, which uses modern tent materials coupled with a novel trap design. This provides an efficacious, a non-labor-intensive, and a safe method for vector collection. In these initial studies, we found it collected an average of 27.7 Anopheles gambiae s.l. per trap per night in rural villages in southeastern Senegal, and 43.8 Culex group Vper trap per night in the semiurban town of Kedougou, Senegal. In direct comparisons with HLC, the tent was not statistically different for collection of Culex quinquefasciatus in crepuscular sampling, but was significantly less efficacious at trapping the highly motile dusk-biter Aedes aegypti. These studies suggest that the Infoscitex tent is a viable and safe alternative to HLC for Anopheles and Culex sampling in areas of high vector-borne disease infection risk.

Observation of blood motion in the internal jugular vein by contact and contactless photoplethysmography during physiological testing: case studies.

Central venous pressure is an estimate of right atrial pressure and is often used to assess hemodynamic status. However, since it is measured invasively, non-invasive alternatives would be of great utility. The aim of this preliminary study was a) to investigate whether photoplethysmography (PPG) can be used to characterize venous system fluid motion and b) to find the model for venous blood volume modulations. For this purpose, we monitored the internal jugular veins using contact (cPPG) and video PPG during clinically validated physiological tests: abdominojugular test (AJT) and breath holding (BH). Video PPG and cPPG signals were captured simultaneously on the left and right sides of the neck, respectively. ECG was also captured using the same clinical monitor as cPPG. Two volunteers underwent AJT and BH with head up/down, each with: baseline (15s), experiment (15s), and recovery (15s). Video PPG was split into remote PPG (rPPG) and micromotion detection. All signal modalities were significantly affected by physiological testing. Moreover, cPPG and micromotion waveforms exhibited primary features of jugular vein waveforms and, therefore, have great potential for venous blood flow monitoring. Specifically, remote patient monitoring applications may be enabled by this methodology, facilitating physical collection without a specially trained care provider.

Pulmonary Hypertension Detection Non-Invasively at Point-of-Care Using a Machine-Learned Algorithm.

Artificial intelligence, particularly machine learning, has gained prominence in medical research due to its potential to develop non-invasive diagnostics. Pulmonary hypertension presents a diagnostic challenge due to its heterogeneous nature and similarity in symptoms to other cardiovascular conditions. Here, we describe the development of a supervised machine learning model using non-invasive signals (orthogonal voltage gradient and photoplethysmographic) and a hand-crafted library of 3298 features. The developed model achieved a sensitivity of 87% and a specificity of 83%, with an overall Area Under the Receiver Operator Characteristic Curve (AUC-ROC) of 0.93. Subgroup analysis showed consistent performance across genders, age groups and classes of PH. Feature importance analysis revealed changes in metrics that measure conduction, repolarization and respiration as significant contributors to the model. The model demonstrates promising performance in identifying pulmonary hypertension, offering potential for early detection and intervention when embedded in a point-of-care diagnostic system.

Development of a Non-Invasive Machine-Learned Point-of-Care Rule-Out Test for Coronary Artery Disease.

The current standard of care for coronary artery disease (CAD) requires an intake of radioactive or contrast enhancement dyes, radiation exposure, and stress and may take days to weeks for referral to gold-standard cardiac catheterization. The CAD diagnostic pathway would greatly benefit from a test to assess for CAD that enables the physician to rule it out at the point of care, thereby enabling the exploration of other diagnoses more rapidly. We sought to develop a test using machine learning to assess for CAD with a rule-out profile, using an easy-to-acquire signal (without stress/radiation) at the point of care. Given the historic disparate outcomes between sexes and urban/rural geographies in cardiology, we targeted equal performance across sexes in a geographically accessible test. Noninvasive photoplethysmogram and orthogonal voltage gradient signals were simultaneously acquired in a representative clinical population of subjects before invasive catheterization for those with CAD (gold-standard for the confirmation of CAD) and coronary computed tomographic angiography for those without CAD (excellent negative predictive value). Features were measured from the signal and used in machine learning to predict CAD status. The machine-learned algorithm achieved a sensitivity of 90% and specificity of 59%. The rule-out profile was maintained across both sexes, as well as all other relevant subgroups. A test to assess for CAD using machine learning on a noninvasive signal has been successfully developed, showing high performance and rule-out ability. Confirmation of the performance on a large clinical, blinded, enrollment-gated dataset is required before implementation of the test in clinical practice.

Clinical Validation of a Machine-Learned, Point-of-Care System to IDENTIFY Functionally Significant Coronary Artery Disease.

Many clinical studies have shown wide performance variation in tests to identify coronary artery disease (CAD). Coronary computed tomography angiography (CCTA) has been identified as an effective rule-out test but is not widely available in the USA, particularly so in rural areas. Patients in rural areas are underserved in the healthcare system as compared to urban areas, rendering it a priority population to target with highly accessible diagnostics. We previously developed a machine-learned algorithm to identify the presence of CAD (defined by functional significance) in patients with symptoms without the use of radiation or stress. The algorithm requires 215 s temporally synchronized photoplethysmographic and orthogonal voltage gradient signals acquired at rest. The purpose of the present work is to validate the performance of the algorithm in a frozen state (i.e., no retraining) in a large, blinded dataset from the IDENTIFY trial. IDENTIFY is a multicenter, selectively blinded, non-randomized, prospective, repository study to acquire signals with paired metadata from subjects with symptoms indicative of CAD within seven days prior to either left heart catheterization or CCTA. The algorithm's sensitivity and specificity were validated using a set of unseen patient signals (n = 1816). Pre-specified endpoints were chosen to demonstrate a rule-out performance comparable to CCTA. The ROC-AUC in the validation set was 0.80 (95% CI: 0.78-0.82). This performance was maintained in both male and female subgroups. At the pre-specified cut point, the sensitivity was 0.85 (95% CI: 0.82-0.88), and the specificity was 0.58 (95% CI: 0.54-0.62), passing the pre-specified endpoints. Assuming a 4% disease prevalence, the NPV was 0.99. Algorithm performance is comparable to tertiary center testing using CCTA. Selection of a suitable cut-point results in the same sensitivity and specificity performance in females as in males. Therefore, a medical device embedding this algorithm may address an unmet need for a non-invasive, front-line point-of-care test for CAD (without any radiation or stress), thus offering significant benefits to the patient, physician, and healthcare system.

Remote photoplethysmography with consumer smartphone reveals temporal differences between glabrous and nonglabrous skin: Pilot in vivo study.

Photoplethysmography (PPG) is a noninvasive optical technology, with applications including vital sign extraction and patient monitoring. The PPG acquisition skin type may be of importance. Skin is either nonglabrous (~90%) or glabrous (~10%). Clinical PPG collection is typically from glabrous (fingerpad), while proliferating wearables collecting PPG, which may perform critical functions like arrythmia detection, often acquire from atypical sites. Glabrous skin has significant differences from nonglabrous, including microcirculation, yet comparisons between their PPG signals have not been well reported. Using a smartphone-based remote/contactless PPG, a pilot dataset was collected from the hands (palmar/dorsal) of five healthy volunteers. The data shows statistically significant lead time (52 ± 36 ms) of glabrous over nonglabrous. Further, a trend of glabrous amplitude increase over nonglabrous (31%) was found. Although our study has a small number of participants, these results further the characterization of PPG skin differences, and can be used to inform development of PPG-based devices.

Semi-field evaluation of a volatile transfluthrin-based intervention reveals efficacy as a spatial repellent and evidence of other modes of action.

Presently, the most common malaria control tools-i.e., long lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS)-are limited to targeting indoor biting and resting behaviors of Anopheles mosquito species. Few interventions are targeted towards malaria control in areas where transmission is driven or persists due to outdoor biting behaviors. This study investigated a volatile pyrethroid-based spatial repellent (VPSR) designed to bridge this gap and provide protection from mosquito bites in outdoor spaces. Southern Province, Zambia, is one such environment where outdoor biting is suspected to contribute to malaria transmission, where people are active in the evening in open-walled outdoor kitchens. This study assessed the VPSR in replica kitchens within a controlled semi-field environment. Endpoints included effects on mosquito host seeking, immediate and delayed mortality, deterrence, blood feeding inhibition, and fertility. Host-seeking was reduced by approximately 40% over the course of nightly releases in chambers containing VPSR devices. Mosquito behavior was not uniform throughout the night, and the modeled effect of the intervention was considerably higher when hourly catch rates were considered. These two observations highlight a limitation of this overnight semi-field design and consideration of mosquito circadian rhythms is recommended for future semi-field studies. Additionally, deterrence and immediate mortality were both observed in treatment chambers, with evidence of delayed mortality and a dose related response. These results demonstrate a primarily personal protective mode of action with possible positive and negative community effects. Further investigation into this primary mode of action will be conducted through a field trial of the same product in nearby communities.

Feasibility of Specular Reflection Imaging for Extraction of Neck Vessel Pressure Waveforms.

Cardiovascular disease (CVD) is a leading cause of death worldwide and was responsible for 31% of all deaths in 2015. Changes in fluid pressures within the vessels of the circulatory system reflect the mechanical function of the heart. The jugular venous (JV) pulse waveform is an important clinical sign for assessing cardiac function. However, technology able to aid evaluation and interpretation are currently lacking. The goal of the current study was to develop a remote monitoring tool that aid clinicians in robust measurements of JV pulse waveforms. To address this need, we have developed a novel imaging modality, Specular Reflection Vascular Imaging (SRVI). The technology uses specular reflection for visualization of skin displacements caused by pressure pulsations in blood vessels. SRVI has been tested on 10 healthy volunteers. 10-seconds videos of the neck illuminated with a diffuse light source were captured at 250 fps. SRVI was able to identify and discriminate skin displacements caused by carotid artery and jugular vein pulsations to extract both carotid artery and jugular vein waveforms, making them easier to be visualized and interpreted. The method provided a 6-fold improvement in signal strength over a comparator remote PPG dataset. The current pilot study is a proof-of-concept demonstration of the potential of Specular Reflection Vascular Imaging for extraction of JV pulse waveforms.

Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data.

Introduction: Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance. Materials and methods: Patients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid. Results: The cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2. Conclusion: This analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions.

Development and validation of a machine learned algorithm to IDENTIFY functionally significant coronary artery disease.

Introduction: Multiple trials have demonstrated broad performance ranges for tests attempting to detect coronary artery disease. The most common test, SPECT, requires capital-intensive equipment, the use of radionuclides, induction of stress, and time off work and/or travel. Presented here are the development and clinical validation of an office-based machine learned algorithm to identify functionally significant coronary artery disease without radiation, expensive equipment or induced patient stress. Materials and methods: The IDENTIFY trial (NCT03864081) is a prospective, multicenter, non-randomized, selectively blinded, repository study to collect acquired signals paired with subject meta-data, including outcomes, from subjects with symptoms of coronary artery disease. Time synchronized orthogonal voltage gradient and photoplethysmographic signals were collected for 230 seconds from recumbent subjects at rest within seven days of either left heart catheterization or coronary computed tomography angiography. Following machine learning on a proportion of these data (N = 2,522), a final algorithm was selected, along with a pre-specified cut point on the receiver operating characteristic curve for clinical validation. An unseen set of subject signals (N = 965) was used to validate the algorithm. Results: At the pre-specified cut point, the sensitivity for detecting functionally significant coronary artery disease was 0.73 (95% CI: 0.68-0.78), and the specificity was 0.68 (0.62-0.74). There exists a point on the receiver operating characteristic curve at which the negative predictive value is the same as coronary computed tomographic angiography, 0.99, assuming a disease incidence of 0.04, yielding sensitivity of 0.89 and specificity of 0.42. Selecting a point at which the positive predictive value is maximized, 0.12, yields sensitivity of 0.39 and specificity of 0.88. Conclusion: The performance of the machine learned algorithm presented here is comparable to common tertiary center testing for coronary artery disease. Employing multiple cut points on the receiver operating characteristic curve can yield the negative predictive value of coronary computed tomographic angiography and a positive predictive value approaching that of myocardial perfusion imaging. As such, a system employing this algorithm may address the need for a non-invasive, no radiation, no stress, front line test, and hence offer significant advantages to the patient, their physician, and healthcare system.