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.
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.
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.
Identification of unilateral aldosterone-producing (Conn's) adenomas has traditionally required lateralization by the invasive and technically difficult procedure of adrenal vein sampling (AVS). ...(11)C-metomidate, a potent inhibitor of adrenal steroidogenic enzymes, is a positron emission tomography (PET) radiotracer that is selectively accumulated by Conn's adenomas.
The objective of the study was to compare the sensitivity and specificity of (11)C-metomidate PET-computed tomography (CT) against the current gold standard of AVS.
The design of the study was within-patient comparison of diagnostic techniques.
The study was conducted at a single center-university teaching hospital.
Thirty-nine patients with primary hyperaldosteronism (PHA) and five with nonfunctioning adenomas (incidentalomas) participated in the study.
The first six PHA patients were studied on three occasions to determine whether steroid pretreatment reduced (11)C-metomidate uptake by normal adrenal. Subsequent patients received dexamethasone for 3 d prior to injection of (11)C-metomidate 150-500 MBq.
Maximum standardized uptake values (SUV(max)) over regions of interest determined from 35-45 min after injection were measured.
Dexamethasone increased tumor to normal adrenal SUV(max) ratio by 25.6 ± 5.0% (P < 0.01). PET-CT visualized subcentimeter adenomas and distinguished hot from cold adenomas within a gland. In 25 patients with PHA and AVS lateralization to the side of an adenoma, SUV(max) over tumor (mean ± sem) of 21.7 ± 1.6 was greater than over normal adrenal, 13.8 ± 0.6 (P = 0.00003); this difference was absent in 10 patients without lateralization on AVS (P = 0.28) and in four of five incidentalomas. On receiver-operator characteristics analysis, an SUV(max) ratio of 1.25:1 provided a specificity of 87% 95% confidence interval (69, 104) and sensitivity of 76% (59, 93); in tumors with SUV(max) greater than 17, the specificity rose to 100%.
(11)C-metomidate PET-CT is a sensitive and specific noninvasive alternative to AVS in the management of PHA.
Control of arbovirus transmission remains focused on vector control through application of insecticides directly to the environment. However, these insecticide applications are often reactive ...interventions that can be poorly-targeted, inadequate for localized control during outbreaks, and opposed due to environmental and toxicity concerns. In this study, we developed endectocide-treated feed as a systemic endectocide for birds to target blood feeding Culex tarsalis, the primary West Nile virus (WNV) bridge vector in the western United States, and conducted preliminary tests on the effects of deploying this feed in the field. In lab tests, ivermectin (IVM) was the most effective endectocide tested against Cx. tarsalis and WNV-infection did not influence mosquito mortality from IVM. Chickens and wild Eurasian collared doves exhibited no signs of toxicity when fed solely on bird feed treated with concentrations up to 200 mg IVM/kg of diet, and significantly more Cx. tarsalis that blood fed on these birds died (greater than 80% mortality) compared to controls (less than 25% mortality). Mosquito mortality following blood feeding correlated with IVM serum concentrations at the time of blood feeding, which dropped rapidly after the withdrawal of treated feed. Preliminary field testing over one WNV season in Fort Collins, Colorado demonstrated that nearly all birds captured around treated bird feeders had detectable levels of IVM in their blood. However, entomological data showed that WNV transmission was non-significantly reduced around treated bird feeders. With further development, deployment of ivermectin-treated bird feed might be an effective, localized WNV transmission control tool.
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.
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.
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.
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.
Abstract Malaria transmission-blocking vaccines (TBVs) are potentially helpful tools for malaria eradication. The standard membrane-feeding assay (SMFA) is considered one of the “gold standard” ...assays for TBV development. However, lack of consensus in reporting results from SMFA has made it very challenging to compare results from different studies. Two main readouts, % inhibition in mean oocyst count per mosquito (TRA) and % inhibition in prevalence of infected mosquitoes (TBA), have been used widely. In this study, we statistically modeled the oocyst data in SMFA using data from 105 independent feeding experiments including 9804 mosquitoes. The model was validated using an independent data set that included 10,790 mosquitoes from 110 feeding studies. The model delineates a relationship between TRA, the mean oocyst count in the control mosquitoes ( mo -contl), and TBA. While TRA was independent from mo -contl, TBA values changed depending on mo -contl. Regardless of monoclonal or polyclonal antibodies tested, there were strong concordances between observed TBA and predicted TBA based on the model using mo -contl and observed TRA. Simulations showed that SMFA with lower true control means had increased uncertainty in TRA estimates. The strong linkage between TBA, TRA and mo -contl inspired creation of a standardized TBA, a model-based TBA standardized to a target control mean, which allows comparison across multiple feeds regardless of mo -contl. This is the first study showing that the observed TBA can be reasonably predicted by mo -contl and the TRA of the test antibody using independent experimental data. This study indicates that TRA should be used to compare results from multiple feeds with different levels of mo -contl. If a measure of TBA is desired, it is better to report standardized TBA rather than observed TBA. These recommendations support rational comparisons of results from different studies, thus benefiting future TBV development.
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.
Visualization and detection of early-stage gynecological malignancies represents a challenge for imaging due to limiting factors including tissue accessibility, device ease of use, and accuracy of ...imaging modalities. In this work, we introduce a miniaturized phased-array ultrasound and photoacoustic endoscopic probe which is capable of providing structural, functional, and molecular data for the characterization of gynecologic disease. The proposed probe consists of a 64-element ultrasound phased-array transducer coupled to a fiber-optic light delivery system for co-registered ultrasound and photoacoustic imaging. The fabricated US and PA imaging endoscope’s diameter is 7.5 mm, allowing for potential passage through the cervical canal and thus an intimate contact with gynecological tissues such as the cervical canal and uterus. The developed endoscopic probe was tested and characterized in a set of tissue-mimicking phantoms. US and PA resolutions were measured experimentally using 200 μm diameter wires, resulting in apparent axial and lateral diameters of 289 μm and 299 μm for US, and 308 μm and 378 μm for PA, respectively. The probe’s abilities to operate in both discrete and integrated illumination/acquisition were tested in gelatin phantoms with embedded optical absorbers with the results demonstrating the ability to acquire volumetric dual-modal US and PA images.
Artemisinin-resistant Plasmodium falciparum parasites are rapidly spreading in Southeast Asia, yet nothing is known about their transmission. This knowledge gap and the possibility that these ...parasites will spread to Africa endanger global efforts to eliminate malaria. Here we produce gametocytes from parasite clinical isolates that displayed artemisinin resistance in patients and in vitro, and use them to infect native and non-native mosquito vectors. We show that contemporary artemisinin-resistant isolates from Cambodia develop and produce sporozoites in two Southeast Asian vectors, Anopheles dirus and Anopheles minimus, and the major African vector, Anopheles coluzzii (formerly Anopheles gambiae M). The ability of artemisinin-resistant parasites to infect such highly diverse Anopheles species, combined with their higher gametocyte prevalence in patients, may explain the rapid expansion of these parasites in Cambodia and neighbouring countries, and further compromise efforts to prevent their global spread.
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