ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial.

BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.

Remote Emotion Recognition Using Continuous-Wave Bio-Radar System.

The Bio-Radar is herein presented as a non-contact radar system able to capture vital signs remotely without requiring any physical contact with the subject. In this work, the ability to use the proposed system for emotion recognition is verified by comparing its performance on identifying fear, happiness and a neutral condition, with certified measuring equipment. For this purpose, machine learning algorithms were applied to the respiratory and cardiac signals captured simultaneously by the radar and the referenced contact-based system. Following a multiclass identification strategy, one could conclude that both systems present a comparable performance, where the radar might even outperform under specific conditions. Emotion recognition is possible using a radar system, with an accuracy equal to 99.7% and an F1-score of 99.9%. Thus, we demonstrated that it is perfectly possible to use the Bio-Radar system for this purpose, which is able to be operated remotely, avoiding the subject awareness of being monitored and thus providing more authentic reactions.

Subjective memory complaints: Prevalence, associated factors and sex differences in the ELSI-Brazil study.

BACKGROUND: Subjective memory complaints (SMCs) are a possible prodrome of cognitive decline but are understudied in low- and middle-income countries (LMIC). We aimed to estimate the prevalence of SMCs in a large, nationally representative sample of older adults from Brazil and to identify sociodemographic and health-related factors that are associated with SMCs independently of objective memory. METHODS: Baseline data (n = 7831) from the ELSI-Brazil study, a national representative sample of adults aged 50 and over. They were asked to rate their memory and then divided into two groups - having or not having SMCs. Logistic regression models were used to estimate the association of demographic characteristics, health related factors, objective memory performance and disability in basic (b-ADL), instrumental (i-ADL), and advanced (a-ADL) activities of daily living associated with SMCs. Whether sex was an effect modifier of the association between age and objective memory performance and SMCs was also tested. RESULTS: Of the sample, 42% (95% CI; 39.9-43.9) had SMCs, and it was higher among women (46.9%) than men (35.9%). SMC prevalence decreased with age among women and increased among men, and for both it decreased with better cognitive performance. Fully adjusted logistic regression model showed that older age, higher education, higher b-ADL scores, and better cognitive performance were associated with decreased SMCs, while being female, with higher number of chronic conditions, higher i-ADL scores, worst self-rated health, and an increased number of depressive symptoms were associated with increased SMCs. However, the interaction test (p < 0.001) confirmed that increased age was associated with decreased SMCs only among women, and that better objective memory performance was associated with decreased SMCs only among men. CONCLUSIONS: SMCs are common in the Brazilian older population and are associated with health and sociodemographic factors, with different patterns between men and women. There is a need for future studies looking at the cognitive trajectory and dementia risk in older adults with subjective cognitive complaints.

3D Antenna Characterization for WPT Applications.

The main goal of this paper is to present a three-dimensional (3D) antenna array to improve the performance of wireless power transmission (WPT) systems, as well as its characterization with over-the-air (OTA) multi-sine techniques. The 3D antenna consists of 15 antenna elements attached to an alternative 3D structure, allowing energy to be transmitted to all azimuth directions at different elevation angles without moving. The OTA multi-sine characterization technique was first utilized to identify issues in antenna arrays. However, in this work, the technique is used to identify which elements of the 3D antenna should operate to transmit the energy in a specific direction. Besides, the 3D antenna design description and its characterization are performed to authenticate its operation. Since 3D antennas are an advantage in WPT applications, the antenna is evaluated in a real WPT scenario to power an RF-DC converter, and experimental results are presented.

Challenges in Resource-Constrained IoT Devices: Energy and Communication as Critical Success Factors for Future IoT Deployment.

Internet of Things (IoT) has been developing to become a free exchange of useful information between multiple real-world devices. Already spread all over the world in the most varied forms and applications, IoT devices need to overcome a series of challenges to respond to the new requirements and demands. The main focus of this manuscript is to establish good practices for the design of IoT devices (i.e., smart devices) with a focus on two main design challenges: power and connectivity. It groups IoT devices in passive, semi-passive, and active, giving details on multiple research topics. Backscatter communication, Wireless Power Transfer (WPT), Energy Harvesting (EH), chipless devices, Simultaneous Wireless Information and Power Transfer (SWIPT), and Wake-Up Radio (WUR) are some examples of the technologies that will be explored in this work.

A Review on Methods for Random Motion Detection and Compensation in Bio-Radar Systems.

The bio-radar system can measure vital signals accurately, by using the Doppler effect principle, which relates the received signal properties to the distance change between the radar antennas and the subject chest-wall. These systems have countless applications, from short range detection to assist in rescue missions, to long-term applications as for the continuous sleeping monitoring. Once the main applications of these systems intend to monitor subjects during long periods of time and under noisy environments, it is impossible to guarantee the patient immobilization, hence its random motion, as well as other clutter sources, will interfere in the acquired signals. Therefore, the signal processing algorithms developed for these applications have been facing several challenges regarding the random motion detection and mitigation. In this paper, an extended review on the already implemented methods is done, considering continuous wave radars. Several sources of random motion are considered, along with different approaches to compensate the distortions caused by them.

Green spaces are not all the same for the provision of air purification and climate regulation services: The case of urban parks.

The growing human population concentrated in urban areas lead to the increase of road traffic and artificial areas, consequently enhancing air pollution and urban heat island effects, among others. These environmental changes affect citizen's health, causing a high number of premature deaths, with considerable social and economic costs. Nature-based solutions are essential to ameliorate those impacts in urban areas. While the mere presence of urban green spaces is pointed as an overarching solution, the relative importance of specific vegetation structure, composition and management to improve the ecosystem services of air purification and climate regulation are overlooked. This avoids the establishment of optimized planning and management procedures for urban green spaces with high spatial resolution and detail. Our aim was to understand the relative contribution of vegetation structure, composition and management for the provision of ecosystem services of air purification and climate regulation in urban green spaces, in particular the case of urban parks. This work was done in a large urban park with different types of vegetation surrounded by urban areas. As indicators of microclimatic effects and of air pollution levels we selected different metrics: lichen diversity and pollutants accumulation in lichens. Among lichen diversity, functional traits related to nutrient and water requirements were used as surrogates of the capacity of vegetation to filter air pollution and to regulate climate, and provide air purification and climate regulation ecosystem services, respectively. This was also obtained with very high spatial resolution which allows detailed spatial planning for optimization of ecosystem services. We found that vegetation type characterized by a more complex structure (trees, shrubs and herbaceous layers) and by the absence of management (pruning, irrigation and fertilization) had a higher capacity to provide the ecosystems services of air purification and climate regulation. By contrast, lawns, which have a less complex structure and are highly managed, were associated to a lower capacity to provide these services. Tree plantations showed an intermediate effect between the other two types of vegetation. Thus, vegetation structure, composition and management are important to optimize green spaces capacity to purify air and regulate climate. Taking this into account green spaces can be managed at high spatial resolutions to optimize these ecosystem services in urban areas and contribute to improve human well-being.

Ecosystem services: Urban parks under a magnifying glass.

Urban areas' population has grown during the last century and it is expected that over 60% of the world population will live in cities by 2050. Urban parks provide several ecosystem services that are valuable to the well-being of city-dwellers and they are also considered a nature-based solution to tackle multiple environmental problems in cities. However, the type and amount of ecosystem services provided will vary with each park vegetation type, even within same the park. Our main goal was to quantify the trade-offs in ecosystem services associated to different vegetation types, using a spatially detailed approach. Rather than relying solely on general vegetation typologies, we took a more ecologically oriented approach, by explicitly considering different units of vegetation structure and composition. This was demonstrated in a large park (44ha) located in the city of Almada (Lisbon metropolitan area, Portugal), where six vegetation units were mapped in detail and six ecosystem services were evaluated: carbon sequestration, seed dispersal, erosion prevention, water purification, air purification and habitat quality. The results showed that, when looking at the park in detail, some ecosystem services varied greatly with vegetation type. Carbon sequestration was positively influenced by tree density, independently of species composition. Seed dispersal potential was higher in lawns, and mixed forest provided the highest amount of habitat quality. Air purification service was slightly higher in mixed forest, but was high in all vegetation types, probably due to low background pollution, and both water purification and erosion prevention were high in all vegetation types. Knowing the type, location, and amount of ecosystem services provided by each vegetation type can help to improve management options based on ecosystem services trade-offs and looking for win-win situations. The trade-offs are, for example, very clear for carbon: tree planting will boost carbon sequestration regardless of species, but may not be enough to increase habitat quality. Moreover, it may also negatively influence seed dispersal service. Informed practitioners can use this ecological knowledge to promote the role of urban parks as a nature-based solution to provide multiple ecosystem services, and ultimately improve the design and management of the green infrastructure. This will also improve the science of Ecosystem Services, acknowledging that the type of vegetation matters for the provision of ecosystem services and trade-offs analysis.

Discovery of ß-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of hepatitis C virus replication.

Discovery of sofosbuvir has radically changed hepatitis C treatment and nucleoside/tide NS5B inhibitors are now viewed as one of the key components in combination therapies with other direct-acting antiviral agents. As part of our program to identify new nucleoside inhibitors of HCV replication, we now wish to report on the discovery of ß-d-2'-deoxy-2'-dichlorouridine nucleotide prodrugs as potent inhibitors of HCV replication. Although, cytidine analogues have long been recognized to be metabolized to both cytidine and uridine triphosphates through the action of cytidine deaminase, uridine analogues are generally believed to produce exclusively uridine triphosphate. Detailed investigation of the intracellular metabolism of our newly discovered uridine prodrugs, as well as of sofosbuvir, has now revealed the formation of both uridine and cytidine triphosphates. This occurs, not only in vitro in cell lines, but also in vivo upon oral dosing to dogs.

Mapping Exposure to Multi-Pollutants Using Environmental Biomonitors-A Multi-Exposure Index.

Atmosphere is a major pathway for transport and deposition of pollutants in the environment. In industrial areas, organic compounds are released or formed as by-products, such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F's). Inorganic chemical elements, including lead and arsenic, are also part of the pollutants mixture, and even in low concentrations may potentially be toxic and carcinogenic. However, assessing the spatial pattern of their deposition is difficult due to high spatial and temporal heterogeneity. Lichens have been used as biomonitors of atmospheric deposition, because these organisms encompass greater spatial detail than air monitoring stations and provide an integration of overall pollution. Based upon the ability of lichens to concentrate pollutants such as PCDD/F and chemical elements, the main objectives of this study were to develop a new semi-quantitative multi-pollutant toxicity exposure index (TEQ-like), derived from risk estimates, in an attempt to correlate several atmospheric pollutants to human exposure levels. The actual pollutant concentrations were measured in the environment, from biomonitors (organisms that integrate multi-pollutants), enabling interpolation and mapping of contaminant deposition within the region. Thus, the TEQ-like index provides a spatial representation not from absolute accumulation of the different pollutants, but from the accumulation weighted by their relative risk. The assessment of environmental human exposure to multi-pollutants through atmospheric deposition may be applied to industries to improve mitigation processes or to health stakeholders to target populations for a comprehensive risk assessment, epidemiological studies, and health recommendations.

Tracking the Spatial Fate of PCDD/F Emissions from a Cement Plant by Using Lichens as Environmental Biomonitors.

In an area with multiple sources of air pollution, it is difficult to evaluate the spatial impact of a minor source. Here, we describe the use of lichens to track minor sources of air pollution. The method was tested by transplanting lichens from a background area to the vicinity of a cement manufacturing plant that uses alternative fuel and is located in a Natural Park in an area surrounded by other important sources of pollution. After 7 months of exposure, the lichens were collected and analyzed for 17 PCDD/F congeners. The PCDD/F profiles of the exposed lichens were dominated by TCDF (50%) and OCDD (38%), which matched the profile of the emissions from the cement plant. The similarity in the profiles was greatest for lichens located northeast of the plant (i.e., in the direction of the prevailing winds during the study period), allowing us to evaluate the spatial impact of this source. The best match was found for sites located on the tops of mountains whose slopes faced the cement plant. Some of the sites with highest influence of the cement plant were the ones with the highest concentrations, whereas others were not. Thus, our newly developed lichen-based method provides a tool for tracking the spatial fate of industrially emitted PCDD/Fs regardless of their concentrations. The results showed that the method can be used to validate deposition models for PCDD/F industrial emissions in sites with several sources and characterized by complex orography.

Evaluating green infrastructure in urban environments using a multi-taxa and functional diversity approach.

Forested areas within cities host a large number of species, responsible for many ecosystem services in urban areas. The biodiversity in these areas is influenced by human disturbances such as atmospheric pollution and urban heat island effect. To ameliorate the effects of these factors, an increase in urban green areas is often considered sufficient. However, this approach assumes that all types of green cover have the same importance for species. Our aim was to show that not all forested green areas are equal in importance for species, but that based on a multi-taxa and functional diversity approach it is possible to value green infrastructure in urban environments. After evaluating the diversity of lichens, butterflies and other-arthropods, birds and mammals in 31 Mediterranean urban forests in south-west Europe (Almada, Portugal), bird and lichen functional groups responsive to urbanization were found. A community shift (tolerant species replacing sensitive ones) along the urbanization gradient was found, and this must be considered when using these groups as indicators of the effect of urbanization. Bird and lichen functional groups were then analyzed together with the characteristics of the forests and their surroundings. Our results showed that, contrary to previous assumptions, vegetation density and more importantly the amount of urban areas around the forest (matrix), are more important for biodiversity than forest quantity alone. This indicated that not all types of forested green areas have the same importance for biodiversity. An index of forest functional diversity was then calculated for all sampled forests of the area. This could help decision-makers to improve the management of urban green infrastructures with the goal of increasing functionality and ultimately ecosystem services in urban areas.

Non-Uniform Microstrip Antenna Array for DSRC in Single-Lane Structures.

Vehicular communications have been subject to a great development in recent years, with multiple applications, such as electronic payments, improving the convenience and comfort of drivers. Its communication network is supported by dedicated short range communications (DSRC), a system composed of onboard units (OBU) and roadside units (RSU). A recently conceived different set-up for the tolling infrastructures consists of placing them in highway access roads, allowing a number of benefits over common gateway infrastructures, divided into several lanes and using complex systems. This paper presents an antenna array whose characteristics are according to the DSRC standards. Additionally, the array holds an innovative radiation pattern adjusted to the new approach requirements, with an almost uniform wide beamwidth along the road width, negligible side lobes, and operating in a significant bandwidth.

Smart Coat with a Fully-Embedded Textile Antenna for IoT Applications.

The Internet of Things (IoT) scenario is strongly related with the advance of the development of wireless sensor networks (WSN) and radio frequency identification (RFID) systems. Additionally, in the WSN context, for a continuous feed, the integration of textile antennas for energy harvesting into smart clothing is a particularly interesting solution when the replacement of batteries is not easy to practice, such as in wearable devices. This paper presents the E-Caption: Smart and Sustainable Coat. It has an embedded dual-band textile antenna for electromagnetic energy harvesting, operating at global system for mobile communication (GSM) 900 and digital cellular system (DCS) 1800 bands. This printed antenna is fully integrated, as its dielectric is the textile material composing the coat itself. The E-Caption illustrates the innovative concept of textile antennas that can be manipulated as simple emblems. Seven prototypes of these "emblem" antennas, manufactured by lamination and embroidering techniques are also presented. It is shown that the orientation of the conductive fabric does not influence the performance of the antenna. It is also shown that the direction and number of the stitches in the embroidery may influence the performance of the antenna. Moreover, the comparison of results obtained before and after the integration of the antenna into cloth shows the integration does not affect the behavior of the antenna.

Disentangling natural and anthropogenic sources of atmospheric sulfur in an industrial region using biomonitors.

Despite reductions in atmospheric sulfur (S) concentrations due to abatement policies in some countries, modeling the dispersion of this pollutant and disentangling anthropogenic sources from natural ones is still of great concern. Lichens have been used as biomonitors of the impacts of S for over 40 years, but their potential as source-tracers of specific sources, including natural ones, remains unexplored. In fact, few attempts have been made to try to distinguish and spatially model different sources of S using lichens. We have measured S concentrations and isotopic values in lichens within an industrial coastal region where different sources of S, natural and anthropogenic, interplay. We detected a prevailing influence of natural sea-originated S that mixed with anthropogenic sources of S. We were then able to disentangle the sources of S, by removing the ocean influence on S isotopic values, enabling us to model the impact of different anthropogenic sources on S deposition and highlighting the potential use of lichens to evaluate the weight of different types of anthropogenic sources.

Microscale is key to model current and future Maritime Antarctic vegetation.

Despite being one of the most pristine regions in the world, Antarctica is currently also one of the most vulnerable to climate change. Antarctic vegetation comprises mostly lichens and bryophytes, complemented in some milder regions of Maritime Antarctica by two vascular plant species. Shifts in the spatial patterns of these three main vegetation groups have already been observed in response to climate change, highlighting the urgent need for the development of comprehensive large-scale ecological models of the effects of climate change. Besides climate, Antarctic terrestrial vegetation is also strongly influenced by non-climatic microscale conditions related to abiotic and biotic factors. Nevertheless, the quantification of their importance in determining vegetation patterns remains unclear. The objective of this work was to quantify the importance of abiotic and biotic microscale conditions in determining the spatial cover patterns of the major functional types, lichens, vascular plants and bryophytes, explicitly determining the likely confinement of each functional type to the microscale conditions, i.e., their ecological niche. Microscale explained >60 % of the spatial variation of lichens and bryophytes and 30 % of vascular plants, with the niche analysis suggesting that each of the three functional types may be likely confined to specific microscale conditions in the studied gradient. Models indicate that the main microscale ecological filters are abiotic but show the potential benefits of including biotic variables and point to the need for further clarification of vegetation biotic interactions' role in these ecosystems. Altogether, these results point to the need for the inclusion of microscale drivers in ecological models to track and forecast climate change effects, as they are crucial to explain present vegetation patterns in response to climate, and for the interpretation of ecological model results under a climate change perspective.

A novel portable anechoic chamber using ultra-thin 2D microwave absorber for industrial 5.0.

In this paper, the authors, for the first time, have shown the use of 2D conformal microwave absorbing material (MAM) in the design and fabrication of a portable Anechoic chamber (AC). The MAM is fabricated on the transparent and conductive metal oxide layer named indium-tin-oxide (ITO) with Polyethylene terephthalate as the substrate and the ground plane for zero transmission having overall thickness of 0.012 λ where λ is calculated at 0.7 GHz. The MAM is characterized for 0.7 to 18 GHz for both TE- and TM-polarisation and oblique incidence. High sheet resistance, dipole-like resonance structure patterned on the ITO, and the air-spacing between the layers is optimized to achieve broadband absorption. The MAM is used to line the six sides of the rectangular anechoic chamber having inner dimensions of: (L × W × H: 850 × 650 × 720 mm3). The return loss (RL), gain, and radiation pattern of three antenna working at 1.56, 2.43, and 4.93 GHz are analyzed inside the AC. The measurement results for all frequencies very well match with the simulation studies, thus validating and opening the door for the future use of ultra-thin and planar MAM in the AC.

Determinants of multimorbidity in low- and middle-income countries: A systematic review of longitudinal studies and discovery of evidence gaps.

Multimorbidity-the coexistence of at least two chronic health conditions within the same individual-is an important global health challenge. In high-income countries (HICs), multimorbidity is dominated by non-communicable diseases (NCDs); whereas, the situation may be different in low- and middle-income countries (LMICs), where chronic communicable diseases remain prominent. The aim of this systematic review was to identify determinants (including risk and protective factors) and potential mechanisms underlying multimorbidity from published longitudinal studies across diverse population-based or community-dwelling populations in LMICs. We systematically searched three electronic databases (Medline, Embase, and Global Health) using pre-defined search terms and selection criteria, complemented by hand-searching. All titles, abstracts, and full texts were independently screened by two reviewers from a pool of four researchers. Data extraction and reporting were according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality and risk of bias assessment was performed using the Newcastle-Ottawa Scale for cohort studies. Data were summarized using narrative synthesis. The search yielded 1782 records. Of the 52 full-text articles included for review, 8 longitudinal population-based studies were included for final data synthesis. Almost all studies were conducted in Asia, with only one from South America and none from Africa. All studies were published in the last decade, with half published in the year 2021. The definitions used for multimorbidity were heterogeneous, including 3-16 chronic conditions per study. The leading chronic conditions were heart disease, stroke, and diabetes, and there was a lack of consideration of mental health conditions (MHCs), infectious diseases, and undernutrition. Prospectively evaluated determinants included socio-economic status, markers of social inequities, childhood adversity, lifestyle behaviors, obesity, dyslipidemia, and disability. This review revealed a paucity of evidence from LMICs and a geographical bias in the distribution of multimorbidity research. Longitudinal research into epidemiological aspects of multimorbidity is warranted to build up scientific evidence in regions beyond Asia. Such evidence can provide a detailed picture of disease development, with important implications for community, clinical, and interventions in LMICs. The heterogeneity in study designs, exposures, outcomes, and statistical methods observed in the present review calls for greater methodological standardisation while conducting epidemiological studies on multimorbidity. The limited evidence for MHCs, infectious diseases, and undernutrition as components of multimorbidity calls for a more comprehensive definition of multimorbidity globally.

Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine.

Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.